ANGPTL4: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
m →‎Clinical significance: task, replaced: Mol Ther. → Mol. Ther.
No edit summary
Line 15: Line 15:
== Clinical significance ==
== Clinical significance ==


ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness.<ref name="pmid18394990">{{cite journal |vauthors=Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, Massagué J | title = TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4 | journal = Cell | volume = 133 | issue = 1 | pages = 66–77 | year = 2008 | pmid = 18394990 | doi = 10.1016/j.cell.2008.01.046 | pmc=2390892}}</ref><ref name="pmid21937683">{{cite journal |vauthors=Kim SH, Park YY, Kim SW, Lee JS, Wang D, DuBois RN | title = ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression | journal = Cancer Res. | volume = 71 | pages = 7010–7020 | year = 2011 | pmid = 21937683 | doi = 10.1158/0008-5472.CAN-11-1262 | issue=22 | pmc=3217078}}</ref><ref name="pmid23208498">{{cite journal |vauthors=Adhikary T, Brandt DT, Kaddatz K, Stockert J, Naruhn S, Meissner W, Finkernagel F, Obert J, Lieber S, Scharfe M, Jarek M, Toth PM, Scheer F, Diederich WE, Reinartz S, Grosse R, Müller-Brüsselbach S, Müller R | title = Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion | journal = Oncogene | year = 2012 | pmid = 23208498 | doi = 10.1038/onc.2012.549 | volume=32 | issue=44 | pages=5241–52 | pmc=3938163}}</ref> ANGPTL4 contributes to tumor growth and protects cells from [[anoikis]], a form of [[programmed cell death]] induced when contact-dependent cells detach from the surrounding tissue matrix.<ref name="pmid21397862"/> ANGPTL4 secreted from tumors can bind to [[integrin]]s, activating downstream signaling and leading to the production of [[superoxide]] to promote [[tumorigenesis]].<ref name="pmid22661548">{{cite journal |vauthors=Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS | title = Emerging Roles of Angiopoietin-like 4 in Human Cancer | journal = Mol. Cancer Res. | volume = 10 | issue = 6 | pages = 1–12 | year = 2012 | pmid = 22661548 | doi=10.1158/1541-7786.MCR-11-0519}}</ref> ANGPTL4 disrupts endothelial [[cell junction]]s by directly interacting with integrin, [[VE-cadherin]] and [[CLDN5|claudin-5]] in a sequential manner to facilitate [[metastasis]].<ref name="pmid21841165">{{cite journal |vauthors=Huang RL, Teo Z, Chong HC, Zhu P, Tan MJ, Tan CK, Lam CR, Sng MK, Leong DT, Tan SM, Kersten S, Ding JL, Li HY, Tan NS | title = ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters | journal = Blood | volume = 118 | issue = 14 | pages = 3990–4002| year = 2011 | pmid = 21841165 | doi = 10.1182/blood-2011-01-328716}}</ref> ANGPTL4 functions as a [[matricellular protein]]<ref name="pmid22481923">{{cite journal |vauthors=Chong HC, Tan CK, Huang RL, Tan NS | title = Matricellular proteins: a sticky affair with cancers | journal = J. Oncol. | volume = 2012 | pages = 351089 |date=Feb 2012 | pmid = 22481923 | doi = 10.1155/2012/351089 | pmc = 3306981 }}</ref> to facilitate skin wound healing. ANGPTL4-deficient mice exhibit delayed wound reepithelialization with impaired [[keratinocyte]] migration, angiogenesis and altered inflammatory response.<ref name="pmid20952587">{{cite journal |vauthors=Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Lam CR, Yau YH, Tan CK, Huang RL, Tan SM, Tang MB, Ding JL, Kersten S, Tan NS | title = Angiopoietin-like 4 interacts with integrins beta1 and beta5 to modulate keratinocyte migration | journal = Am J Pathol | volume = 177 | issue = 6 | pages = 2791–2803 | year = 2010 | pmid = 20952587 | doi = 10.2353/ajpath.2010.100129 | pmc=2993291}}</ref><ref name="pmid20729546">{{cite journal |vauthors=Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Tan CK, Huang RL, Sze SK, Tang MB, Ding JL, Kersten S, Tan NS | title = Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing | journal = J Biol Chem | volume = 285 | issue = 43 | pages = 32999–33009 | year = 2010 | pmid = 20729546 | doi = 10.1074/jbc.M110.108175 | pmc=2963335}}</ref> ANGPTL4 induces [[nitric oxide]] production through an integrin/JAK/STAT3-mediated upregulation of [[iNOS]] expression in wound epithelia, and enhances angiogenesis to accelerate wound healing in diabetic mice.<ref name="pmid24903577">{{cite journal |vauthors=Chong HC, Chan JS, Goh CQ, Gounko NV, Luo B, Wang X, Foo S, Wong MT, Choong C, Kersten S, Tan NS | title = Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice | journal = Mol. Ther. | year=2014 | pmid=24903577 | pmc = 4435481 | doi = 10.1038/mt.2014.102 | volume=22 | issue = 9 | pages=1593–1604}}</ref> Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic.<ref name="pmid26670924">{{cite journal |vauthors=Mousavizadeh R, Scott A, Lu A, Ardekani GS, Behzad H, Lundgreen K, Ghaffari M, McCormack RG, Duronio V | title = Angiopoietin-like 4 (ANGPTL4) promotes angiogenesis in tendon and is increased in cyclically loaded tendon fibroblasts| journal = J. Physiol. | year=2015 | pmid=26670924 | pmc = 4887665| doi = 10.1113/JP271752 | volume=594 | issue = 11| pages=2971–83}}</ref> ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. The expression of ANGPTL4 was increased in the aqueous and vitreous of proliferative diabetic retinopathy patients and localized to areas of retinal neovascularization.<ref name="pmid26039997">{{cite journal |vauthors=Babapoor-Farrokhran S, Jee K, Puchner B, Hassan SJ, Xin X, Rodrigues M, Kashiwabuchi F, Ma T, Hu K, Deshpande M, Daoud Y, Solomon S, Wenick A, Lutty GA, Semenza GL, Montaner S, Sodhi A | title = Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy| journal = Proc Natl Acad Sci U S A | year=2015 | pmid=26039997 | doi = 10.1073/pnas.1423765112 | volume=112 | issue = 23| pages=E3030–9 | pmc=4466723}}</ref>
ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness.<ref name="pmid18394990">{{cite journal |vauthors=Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, Massagué J | title = TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4 | journal = Cell | volume = 133 | issue = 1 | pages = 66–77 | year = 2008 | pmid = 18394990 | doi = 10.1016/j.cell.2008.01.046 | pmc=2390892}}</ref><ref name="pmid21937683">{{cite journal |vauthors=Kim SH, Park YY, Kim SW, Lee JS, Wang D, DuBois RN | title = ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression | journal = Cancer Res. | volume = 71 | pages = 7010–7020 | year = 2011 | pmid = 21937683 | doi = 10.1158/0008-5472.CAN-11-1262 | issue=22 | pmc=3217078}}</ref><ref name="pmid23208498">{{cite journal |vauthors=Adhikary T, Brandt DT, Kaddatz K, Stockert J, Naruhn S, Meissner W, Finkernagel F, Obert J, Lieber S, Scharfe M, Jarek M, Toth PM, Scheer F, Diederich WE, Reinartz S, Grosse R, Müller-Brüsselbach S, Müller R | title = Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion | journal = Oncogene | year = 2012 | pmid = 23208498 | doi = 10.1038/onc.2012.549 | volume=32 | issue=44 | pages=5241–52 | pmc=3938163}}</ref> ANGPTL4 contributes to tumor growth and protects cells from [[anoikis]], a form of [[programmed cell death]] induced when contact-dependent cells detach from the surrounding tissue matrix.<ref name="pmid21397862"/> ANGPTL4 secreted from tumors can bind to [[integrin]]s, activating downstream signaling and leading to the production of [[superoxide]] to promote [[tumorigenesis]].<ref name="pmid22661548">{{cite journal |vauthors=Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS | title = Emerging Roles of Angiopoietin-like 4 in Human Cancer | journal = Mol. Cancer Res. | volume = 10 | issue = 6 | pages = 1–12 | year = 2012 | pmid = 22661548 | doi=10.1158/1541-7786.MCR-11-0519}}</ref> ANGPTL4 disrupts endothelial [[cell junction]]s by directly interacting with integrin, [[VE-cadherin]] and [[CLDN5|claudin-5]] in a sequential manner to facilitate [[metastasis]].<ref name="pmid21841165">{{cite journal |vauthors=Huang RL, Teo Z, Chong HC, Zhu P, Tan MJ, Tan CK, Lam CR, Sng MK, Leong DT, Tan SM, Kersten S, Ding JL, Li HY, Tan NS | title = ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters | journal = Blood | volume = 118 | issue = 14 | pages = 3990–4002| year = 2011 | pmid = 21841165 | doi = 10.1182/blood-2011-01-328716}}</ref> ANGPTL4, specifically the C-terminal fragment (cANGPTL4), is a key player that coordinates an increase in cellular energy flux crucial for epithelial-mesenchymal transition [[EMT]] via an ANGPTL4:YWHAG (14-3-3γ) signaling axis.<ref name="pmid28745316">{{cite journal |vauthors=Teo Z, Sng MK, Chan JSK, Lim MMK, Li Y, Li L, Phua T, Lee JYH, Tan ZW, Zhu P, Tan NS | title = Elevation of adenylate energy charge by angiopoietin-like 4 enhances epithelial-mesenchymal transition by inducing 14-3-3γ expression | journal = Oncogene | volume = 36 | issue = 46 | pages = 6408-6419 | year = 2017 | pmid = 28745316 | doi = 10.1038/onc.2017.244 | pmc=5701092}}</ref><ref name="pmid28641978">{{cite journal |vauthors=Tan ZW, Teo Z, Tan C, Choo CC, Loo WS, Song Y, Tam ZY, Ng SP, Koh HZ, Ng YS, Shochat SG, Yau YH, Zhu P, Tan NS | title = ANGPTL4 T266M variant is associated with reduced cancer invasiveness | journal = Biochim Biophys Acta Mol Cell Res. | volume = 1864 | issue = 10 | pages = 1525-1536 | year = 2017 | pmid = 28641978 | doi = 10.1016/j.bbamcr.2017.06.010}}</ref> The ANGPTL4:YWHAG signaling axis confers metabolic flexibility and enhances EMT competency through interaction with specific phosphorylation signals on target proteins. A direct consequence is that ANGPTL4 secures ample cellular energy to fuel multiple [[ABC transporters]] to confer EMT-mediated chemoresistance. <ref name="pmid30342537">{{cite journal |vauthors=Lim MMK, Wee JWK, Soong JC, Chua D, Tan WR, Lizwan M, Li Y, Teo Z, Goh WWB, Zhu P, Tan NS | title = Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs | journal = Mol. Cancer | volume = 17 | issue = 1 | pages = 152 | year = 2018 | pmid = 30342537 | doi=10.1186/s12943-018-0904-z | pmc=6195749}}</ref>
ANGPTL4 functions as a [[matricellular protein]]<ref name="pmid22481923">{{cite journal |vauthors=Chong HC, Tan CK, Huang RL, Tan NS | title = Matricellular proteins: a sticky affair with cancers | journal = J. Oncol. | volume = 2012 | pages = 351089 |date=Feb 2012 | pmid = 22481923 | doi = 10.1155/2012/351089 | pmc = 3306981 }}</ref> to facilitate skin wound healing. ANGPTL4-deficient mice exhibit delayed wound reepithelialization with impaired [[keratinocyte]] migration, angiogenesis and altered inflammatory response.<ref name="pmid20952587">{{cite journal |vauthors=Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Lam CR, Yau YH, Tan CK, Huang RL, Tan SM, Tang MB, Ding JL, Kersten S, Tan NS | title = Angiopoietin-like 4 interacts with integrins beta1 and beta5 to modulate keratinocyte migration | journal = Am J Pathol | volume = 177 | issue = 6 | pages = 2791–2803 | year = 2010 | pmid = 20952587 | doi = 10.2353/ajpath.2010.100129 | pmc=2993291}}</ref><ref name="pmid20729546">{{cite journal |vauthors=Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Tan CK, Huang RL, Sze SK, Tang MB, Ding JL, Kersten S, Tan NS | title = Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing | journal = J Biol Chem | volume = 285 | issue = 43 | pages = 32999–33009 | year = 2010 | pmid = 20729546 | doi = 10.1074/jbc.M110.108175 | pmc=2963335}}</ref> ANGPTL4 induces [[nitric oxide]] production through an integrin/JAK/STAT3-mediated upregulation of [[iNOS]] expression in wound epithelia, and enhances angiogenesis to accelerate wound healing in diabetic mice.<ref name="pmid24903577">{{cite journal |vauthors=Chong HC, Chan JS, Goh CQ, Gounko NV, Luo B, Wang X, Foo S, Wong MT, Choong C, Kersten S, Tan NS | title = Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice | journal = Mol. Ther. | year=2014 | pmid=24903577 | pmc = 4435481 | doi = 10.1038/mt.2014.102 | volume=22 | issue = 9 | pages=1593–1604}}</ref> ANGPTL4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression.<ref name="pmid28740178">{{cite journal |vauthors=Teo Z, Chan JSK, Chong HC, Sng MK, Choo CC, Phua GZM, Teo DJR, Zhu P, Choong C, Wong MTC, Tan NS | title = Angiopoietin-like 4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression | journal = Sci. Rep. | year=2017 | pmid=28740178 | doi = 10.1038/s41598-017-05869-x | volume=7 | issue = 1 | pages=6303 | pmc=5524754}}</ref> ANGPTL4 is capable of reversing the fibroblast-to-myofibroblast differentiation induced aligned electrospun fibrous substrates.<ref name="pmid30901162">{{cite journal |vauthors=Chen H, Lui YS, Tan ZW, Lee JYH, Tan NS, Tan LP | title = Migration and Phenotype Control of Human Dermal Fibroblasts by Electrospun Fibrous Substrates | journal = Adv Healthc Mater. | volume = 8 | issue = 9 | pages = e1801378 | year = 2019 | pmid = 30901162 | doi = 10.1002/adhm.201801378}}</ref> Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic.<ref name="pmid26670924">{{cite journal |vauthors=Mousavizadeh R, Scott A, Lu A, Ardekani GS, Behzad H, Lundgreen K, Ghaffari M, McCormack RG, Duronio V | title = Angiopoietin-like 4 (ANGPTL4) promotes angiogenesis in tendon and is increased in cyclically loaded tendon fibroblasts| journal = J. Physiol. | year=2015 | pmid=26670924 | pmc = 4887665| doi = 10.1113/JP271752 | volume=594 | issue = 11| pages=2971–83}}</ref> ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. The expression of ANGPTL4 was increased in the aqueous and vitreous of proliferative diabetic retinopathy patients and localized to areas of retinal neovascularization.<ref name="pmid26039997">{{cite journal |vauthors=Babapoor-Farrokhran S, Jee K, Puchner B, Hassan SJ, Xin X, Rodrigues M, Kashiwabuchi F, Ma T, Hu K, Deshpande M, Daoud Y, Solomon S, Wenick A, Lutty GA, Semenza GL, Montaner S, Sodhi A | title = Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy| journal = Proc Natl Acad Sci U S A | year=2015 | pmid=26039997 | doi = 10.1073/pnas.1423765112 | volume=112 | issue = 23| pages=E3030–9 | pmc=4466723}}</ref>


ANGPTL4 has been established as a potent inhibitor of serum [[triglyceride]] (TG) clearance, causing elevation of serum TG levels via inhibition of the enzyme [[lipoprotein lipase]] (LPL). Biochemical studies indicate that ANGPTL4 disables LPL partly by dissociating the catalytically active LPL dimer into inactive LPL monomers.<ref name="pmid17088546">{{cite journal |vauthors=Sukonina V, Lookene A, Olivecrona T, Olivecrona G | title = Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue | journal = Proc. Natl. Acad. Sci. U.S.A. | pmid = 17088546 | doi = 10.1073/pnas.0604026103| volume= 103| issue=46 | year=2006 | pages=17450–5 | pmc=1859949}}</ref> However, evidence also suggests that ANGPTL4 functions as a conventional, non-competitive inhibitor that binds to LPL to prevent the hydrolysis of substrate as part of reversible mechanism.<ref name="pmid23960078">{{cite journal |vauthors=Lafferty MJ, Bradford KC, Erie DA, Neher SB | title = Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation | journal = J. Biol. Chem. | pmid = 23960078 | doi = 10.1074/jbc.M113.497602| volume= 288| issue= 40|date=Jul 2013 | pages=28524–34 | pmc=3789953}}</ref> As a consequence, ANGPTL4 [[knockout mouse|knockout mice]] have reduced serum triglyceride levels, whereas the opposite is true for mice over-expressing ANGPTL4. ANGPTL4 suppresses foam cell formation to reduce [[atherosclerosis]] development.<ref name="pmid23640487">{{cite journal |vauthors=Georgiadi A, Wang Y, Stienstra R, Tjeerdema N, Janssen A, Stalenhoef A, van der Vliet JA, de Roos A, Tamsma JT, Smit JW, Tan NS, Müller M, Kersten S | title = Overexpression of Angiopoietin-like Protein 4 Protects Against Atherosclerosis | journal = Arterioscler. Thromb. Vasc. Biol. | pmid = 23640487 | doi = 10.1161/ATVBAHA.113.301698| volume= 33| issue= 7|date=Oct 2013 | pages=1529–37}}</ref> The reduction in LPL activity in [[adipose tissue]] during [[fasting]] is likely caused by increased local production of ANGPTL4. In other tissues such as heart, production of ANGPTL4 is stimulated by [[fatty acid]]s and may serve to protect cells against excess fat uptake.<ref name="pmid20378851">{{cite journal |vauthors=Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten MV, van Bilsen M, Desvergne B, Müller M, Kersten S | title = Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress | journal = Circ. Res. | volume=106 | issue = 11 | pages=1712–1721 | year=2010 | pmid=20378851 | doi = 10.1161/CIRCRESAHA.110.217380}}</ref> ANGPTL4 is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise. ANGPTL4 in nonexercising muscle presumably leads to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. The induction of ANGPTL4 in exercising muscle likely is counteracted via [[AMP-activated protein kinase]] (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles.<ref name="pmid24591600">{{cite journal |vauthors=Catoire M, Alex S, Paraskevopulos N, Mattijssen F, Evers-van Gogh I, Schaart G, Jeppesen J, Kneppers A, Mensink M, Voshol PJ, Olivecrona G, Tan NS, Hesselink MK, Berbée JF, Rensen PC, Kalkhoven E, Schrauwen P, Kersten S | title = Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise | journal = Proc Natl Acad Sci U S A | volume=111 | issue = 11 | pages=E1043–52 | year=2014 | pmid=24591600 | doi = 10.1073/pnas.1400889111| pmc=3964070 }}</ref>
ANGPTL4 has been established as a potent inhibitor of serum [[triglyceride]] (TG) clearance, causing elevation of serum TG levels via inhibition of the enzyme [[lipoprotein lipase]] (LPL). Biochemical studies indicate that ANGPTL4 disables LPL partly by dissociating the catalytically active LPL dimer into inactive LPL monomers.<ref name="pmid17088546">{{cite journal |vauthors=Sukonina V, Lookene A, Olivecrona T, Olivecrona G | title = Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue | journal = Proc. Natl. Acad. Sci. U.S.A. | pmid = 17088546 | doi = 10.1073/pnas.0604026103| volume= 103| issue=46 | year=2006 | pages=17450–5 | pmc=1859949}}</ref> However, evidence also suggests that ANGPTL4 functions as a conventional, non-competitive inhibitor that binds to LPL to prevent the hydrolysis of substrate as part of reversible mechanism.<ref name="pmid23960078">{{cite journal |vauthors=Lafferty MJ, Bradford KC, Erie DA, Neher SB | title = Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation | journal = J. Biol. Chem. | pmid = 23960078 | doi = 10.1074/jbc.M113.497602| volume= 288| issue= 40|date=Jul 2013 | pages=28524–34 | pmc=3789953}}</ref> As a consequence, ANGPTL4 [[knockout mouse|knockout mice]] have reduced serum triglyceride levels, whereas the opposite is true for mice over-expressing ANGPTL4. ANGPTL4 suppresses foam cell formation to reduce [[atherosclerosis]] development.<ref name="pmid23640487">{{cite journal |vauthors=Georgiadi A, Wang Y, Stienstra R, Tjeerdema N, Janssen A, Stalenhoef A, van der Vliet JA, de Roos A, Tamsma JT, Smit JW, Tan NS, Müller M, Kersten S | title = Overexpression of Angiopoietin-like Protein 4 Protects Against Atherosclerosis | journal = Arterioscler. Thromb. Vasc. Biol. | pmid = 23640487 | doi = 10.1161/ATVBAHA.113.301698| volume= 33| issue= 7|date=Oct 2013 | pages=1529–37}}</ref> The reduction in LPL activity in [[adipose tissue]] during [[fasting]] is likely caused by increased local production of ANGPTL4. In other tissues such as heart, production of ANGPTL4 is stimulated by [[fatty acid]]s and may serve to protect cells against excess fat uptake.<ref name="pmid20378851">{{cite journal |vauthors=Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten MV, van Bilsen M, Desvergne B, Müller M, Kersten S | title = Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress | journal = Circ. Res. | volume=106 | issue = 11 | pages=1712–1721 | year=2010 | pmid=20378851 | doi = 10.1161/CIRCRESAHA.110.217380}}</ref> ANGPTL4 is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise. ANGPTL4 in nonexercising muscle presumably leads to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. The induction of ANGPTL4 in exercising muscle likely is counteracted via [[AMP-activated protein kinase]] (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles.<ref name="pmid24591600">{{cite journal |vauthors=Catoire M, Alex S, Paraskevopulos N, Mattijssen F, Evers-van Gogh I, Schaart G, Jeppesen J, Kneppers A, Mensink M, Voshol PJ, Olivecrona G, Tan NS, Hesselink MK, Berbée JF, Rensen PC, Kalkhoven E, Schrauwen P, Kersten S | title = Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise | journal = Proc Natl Acad Sci U S A | volume=111 | issue = 11 | pages=E1043–52 | year=2014 | pmid=24591600 | doi = 10.1073/pnas.1400889111| pmc=3964070 }}</ref>


High-throughput RNA sequencing of lung tissue samples from the 1918 and 2009 [[influenza pandemic]] revealed that ANGPTL4 was one of the most significantly upregulated gene.<ref name="pmid23180419">{{cite journal |vauthors=Xiao YL, Kash JC, Beres SB, Sheng ZM, Musser JM, Taubenberger JK | title = High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded autopsy lung tissue sample from the 1918 influenza pandemic | journal = J. Pathol. | pmid = 23180419| doi = 10.1002/path.4145| volume=229 | issue=4 |date=Mar 2013 | pages=535–45 | pmc=3731037}}</ref> Murine influenza infection of the lungs stimulated the expression of ANGPTL4 via a STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Influenza-infected ANGPTL4-knockout mice displayed diminished lung damage and recovered faster from the infection compared to wild-type mice. The treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated pulmonary recovery and improved lung tissue integrity.<ref name="pmid25660016">{{cite journal |vauthors=Li L, Chong HC, Ng SY, Kwok KW, Teo Z, Tan EH, Choo CC, Seet JE, Choi HW, Buist ML, Chow VT, Tan NS | title = Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia | journal = Cell Rep. | volume=10 | issue=5 |pages=654–663 | year=2015 | pmid=25660016 | doi=10.1016/j.celrep.2015.01.011}}</ref>
High-throughput RNA sequencing of lung tissue samples from the 1918 and 2009 [[influenza pandemic]] revealed that ANGPTL4 was one of the most significantly upregulated gene.<ref name="pmid23180419">{{cite journal |vauthors=Xiao YL, Kash JC, Beres SB, Sheng ZM, Musser JM, Taubenberger JK | title = High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded autopsy lung tissue sample from the 1918 influenza pandemic | journal = J. Pathol. | pmid = 23180419| doi = 10.1002/path.4145| volume=229 | issue=4 |date=Mar 2013 | pages=535–45 | pmc=3731037}}</ref> Murine influenza infection of the lungs stimulated the expression of ANGPTL4 via a STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Influenza-infected ANGPTL4-knockout mice displayed diminished lung damage and recovered faster from the infection compared to wild-type mice. The treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated pulmonary recovery and improved lung tissue integrity.<ref name="pmid25660016">{{cite journal |vauthors=Li L, Chong HC, Ng SY, Kwok KW, Teo Z, Tan EH, Choo CC, Seet JE, Choi HW, Buist ML, Chow VT, Tan NS | title = Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia | journal = Cell Rep. | volume=10 | issue=5 |pages=654–663 | year=2015 | pmid=25660016 | doi=10.1016/j.celrep.2015.01.011}}</ref> It was also shown that antibody treatment against ANGPTL4 reduces pulmonary edema and injury in secondary pneumococcal [[pneumonia]].<ref name="pmid31164474">{{cite journal |vauthors=Li L, Foo BJW, Kwok KW, Sakamoto N, Mukae H, Izumikawa K, Mandard S, Quenot JP, Lagrost L, Teh WK, Singh Kohli G, Zhu P, Choi H, Buist ML, Seet JE, Yang L, He F, Kwong Chow VT, Tan NS | title = Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia | journal = mBio | volume = 10 | issue = 3 |pages=pii: e02469-18 | year=2019 | pmid=31164474 | doi=10.1128/mBio.02469-18}}</ref>


==References==
==References==

Revision as of 14:55, 18 June 2019

ANGPTL4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesANGPTL4, ANGPTL2, ARP4, FIAF, HARP, HFARP, NL2, PGAR, TGQTL, UNQ171, pp1158, angiopoietin like 4
External IDsOMIM: 604774, 605910; MGI: 1888999; HomoloGene: 10755; GeneCards: ANGPTL4; OMA:ANGPTL4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

51129

57875

Ensembl

ENSG00000167772

ENSMUSG00000002289

UniProt

Q9BY76

Q9Z1P8

RefSeq (mRNA)

NM_001039667
NM_016109
NM_139314

NM_020581

RefSeq (protein)

NP_001034756
NP_647475

NP_065606

Location (UCSC)Chr 19: 8.36 – 8.37 MbChr 17: 33.99 – 34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Angiopoietin-like 4 is a protein that in human is encoded by the ANGPTL4 gene.[5][6][7] Alternatively spliced transcript variants encoding different isoforms have been described. This gene was previously referred to as ANGPTL2, HFARP, PGAR, or FIAF but has been renamed ANGPTL4.

Structure

This gene is a member of the angiopoietin-like gene family and encodes a glycosylated, secreted protein with a coiled-coil N-terminal domain and a fibrinogen-like C-terminal domain.[8]

Expression

In mice, highest mRNA expression levels of ANGPTL4 are found in white and brown adipose tissue, followed by liver, kidney, muscle and intestine. Human ANGPTL4 is most highly expressed in liver.

Function

Picture depicts role of ANGPTL4 as endogenous inhibitor of lipoprotein lipase and its regulation by fatty acids via Peroxisome Proliferator Activated Receptors

This gene is induced under hypoxic (low oxygen) condition in various cell types and is the target of Peroxisome proliferator-activated receptors. The encoded protein is a serum hormone directly involved in regulating lipid metabolism. The native full length ANGPTL4 can form higher order structures via intermolecular disulfide bonds. The N-terminal region of ANGPTL4 (nANGPTL4) is responsible for its assembly. The full length ANGPTL4 undergoes proteolytic cleavage at the linker region, releasing nANGPTL4 and the monomeric C-terminal portion of ANGPTL4 (cANGPTL4). The nANGPTL4 and cANGPTL4 have different biological functions.[8] Monoclonal antibodies targeting the nANGPTL4[9] and cANGPTL4[10] have been developed to distinguish their functions.

Clinical significance

ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness.[11][12][13] ANGPTL4 contributes to tumor growth and protects cells from anoikis, a form of programmed cell death induced when contact-dependent cells detach from the surrounding tissue matrix.[10] ANGPTL4 secreted from tumors can bind to integrins, activating downstream signaling and leading to the production of superoxide to promote tumorigenesis.[14] ANGPTL4 disrupts endothelial cell junctions by directly interacting with integrin, VE-cadherin and claudin-5 in a sequential manner to facilitate metastasis.[15] ANGPTL4, specifically the C-terminal fragment (cANGPTL4), is a key player that coordinates an increase in cellular energy flux crucial for epithelial-mesenchymal transition EMT via an ANGPTL4:YWHAG (14-3-3γ) signaling axis.[16][17] The ANGPTL4:YWHAG signaling axis confers metabolic flexibility and enhances EMT competency through interaction with specific phosphorylation signals on target proteins. A direct consequence is that ANGPTL4 secures ample cellular energy to fuel multiple ABC transporters to confer EMT-mediated chemoresistance. [18]

ANGPTL4 functions as a matricellular protein[19] to facilitate skin wound healing. ANGPTL4-deficient mice exhibit delayed wound reepithelialization with impaired keratinocyte migration, angiogenesis and altered inflammatory response.[20][21] ANGPTL4 induces nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of iNOS expression in wound epithelia, and enhances angiogenesis to accelerate wound healing in diabetic mice.[22] ANGPTL4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression.[23] ANGPTL4 is capable of reversing the fibroblast-to-myofibroblast differentiation induced aligned electrospun fibrous substrates.[24] Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic.[25] ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. The expression of ANGPTL4 was increased in the aqueous and vitreous of proliferative diabetic retinopathy patients and localized to areas of retinal neovascularization.[26]

ANGPTL4 has been established as a potent inhibitor of serum triglyceride (TG) clearance, causing elevation of serum TG levels via inhibition of the enzyme lipoprotein lipase (LPL). Biochemical studies indicate that ANGPTL4 disables LPL partly by dissociating the catalytically active LPL dimer into inactive LPL monomers.[27] However, evidence also suggests that ANGPTL4 functions as a conventional, non-competitive inhibitor that binds to LPL to prevent the hydrolysis of substrate as part of reversible mechanism.[28] As a consequence, ANGPTL4 knockout mice have reduced serum triglyceride levels, whereas the opposite is true for mice over-expressing ANGPTL4. ANGPTL4 suppresses foam cell formation to reduce atherosclerosis development.[29] The reduction in LPL activity in adipose tissue during fasting is likely caused by increased local production of ANGPTL4. In other tissues such as heart, production of ANGPTL4 is stimulated by fatty acids and may serve to protect cells against excess fat uptake.[30] ANGPTL4 is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise. ANGPTL4 in nonexercising muscle presumably leads to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. The induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles.[31]

High-throughput RNA sequencing of lung tissue samples from the 1918 and 2009 influenza pandemic revealed that ANGPTL4 was one of the most significantly upregulated gene.[32] Murine influenza infection of the lungs stimulated the expression of ANGPTL4 via a STAT3-mediated mechanism. ANGPTL4 enhanced pulmonary tissue leakiness and exacerbated inflammation-induced lung damage. Influenza-infected ANGPTL4-knockout mice displayed diminished lung damage and recovered faster from the infection compared to wild-type mice. The treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated pulmonary recovery and improved lung tissue integrity.[33] It was also shown that antibody treatment against ANGPTL4 reduces pulmonary edema and injury in secondary pneumococcal pneumonia.[34]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000167772 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002289 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kim I, Kim HG, Kim H, Kim HH, Park SK, Uhm CS, Lee ZH, Koh GY (May 2000). "Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis". Biochem J. 346 (Pt 3): 603–10. doi:10.1042/0264-6021:3460603. PMC 1220891. PMID 10698685.
  6. ^ Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spiegelman BM (Jul 2000). "Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation". Mol Cell Biol. 20 (14): 5343–5349. doi:10.1128/MCB.20.14.5343-5349.2000. PMC 85983. PMID 10866690.
  7. ^ Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B, Wahli W (Sep 2000). "Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene". J. Biol. Chem. 275 (37): 28488–93. doi:10.1074/jbc.M004029200. PMID 10862772.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ a b Zhu P, Goh YY, Chin HF, Kersten S, Tan NS (2012). "Angiopoietin-like 4: a decade of research". Biosci. Rep. 32 (3): 211–9. doi:10.1042/BSR20110102. PMID 22458843.
  9. ^ Desai U, Lee EC, Chung K, Gao C, Gay J, Key B, Hansen G, Machajewski D, Platt KA, Sands AT, Schneider M, Van Sligtenhorst I, Suwanichkul A, Vogel P, Wilganowski N, Wingert J, Zambrowicz BP, Landes G, Powell DR (2007). "Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice". Proc Natl Acad Sci U S A. 104 (28): 11766–11771. doi:10.1073/pnas.0705041104. PMC 1913890. PMID 17609370.
  10. ^ a b Zhu P, Tan MJ, Huang RL, Tan CK, Chong HC, Pal M, Lam CR, Boukamp P, Pan JY, Tan SH, Kersten S, Li HY, Ding JL, Tan NS (2011). "Angiopoietin-like 4 protein elevates the prosurvival intracellular O2(-):H2O2 ratio and confers anoikis resistance to tumors". Cancer Cell. 19 (3): 401–415. doi:10.1016/j.ccr.2011.01.018. PMID 21397862.
  11. ^ Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, Massagué J (2008). "TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4". Cell. 133 (1): 66–77. doi:10.1016/j.cell.2008.01.046. PMC 2390892. PMID 18394990.
  12. ^ Kim SH, Park YY, Kim SW, Lee JS, Wang D, DuBois RN (2011). "ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression". Cancer Res. 71 (22): 7010–7020. doi:10.1158/0008-5472.CAN-11-1262. PMC 3217078. PMID 21937683.
  13. ^ Adhikary T, Brandt DT, Kaddatz K, Stockert J, Naruhn S, Meissner W, Finkernagel F, Obert J, Lieber S, Scharfe M, Jarek M, Toth PM, Scheer F, Diederich WE, Reinartz S, Grosse R, Müller-Brüsselbach S, Müller R (2012). "Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion". Oncogene. 32 (44): 5241–52. doi:10.1038/onc.2012.549. PMC 3938163. PMID 23208498.
  14. ^ Tan MJ, Teo Z, Sng MK, Zhu P, Tan NS (2012). "Emerging Roles of Angiopoietin-like 4 in Human Cancer". Mol. Cancer Res. 10 (6): 1–12. doi:10.1158/1541-7786.MCR-11-0519. PMID 22661548.
  15. ^ Huang RL, Teo Z, Chong HC, Zhu P, Tan MJ, Tan CK, Lam CR, Sng MK, Leong DT, Tan SM, Kersten S, Ding JL, Li HY, Tan NS (2011). "ANGPTL4 modulates vascular junction integrity by integrin signaling and disruption of intercellular VE-cadherin and claudin-5 clusters". Blood. 118 (14): 3990–4002. doi:10.1182/blood-2011-01-328716. PMID 21841165.
  16. ^ Teo Z, Sng MK, Chan J, Lim M, Li Y, Li L, Phua T, Lee J, Tan ZW, Zhu P, Tan NS (2017). "Elevation of adenylate energy charge by angiopoietin-like 4 enhances epithelial-mesenchymal transition by inducing 14-3-3γ expression". Oncogene. 36 (46): 6408–6419. doi:10.1038/onc.2017.244. PMC 5701092. PMID 28745316. {{cite journal}}: Vancouver style error: initials in name 3 (help)
  17. ^ Tan ZW, Teo Z, Tan C, Choo CC, Loo WS, Song Y, Tam ZY, Ng SP, Koh HZ, Ng YS, Shochat SG, Yau YH, Zhu P, Tan NS (2017). "ANGPTL4 T266M variant is associated with reduced cancer invasiveness". Biochim Biophys Acta Mol Cell Res. 1864 (10): 1525–1536. doi:10.1016/j.bbamcr.2017.06.010. PMID 28641978.
  18. ^ Lim M, Wee J, Soong JC, Chua D, Tan WR, Lizwan M, Li Y, Teo Z, Goh W, Zhu P, Tan NS (2018). "Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs". Mol. Cancer. 17 (1): 152. doi:10.1186/s12943-018-0904-z. PMC 6195749. PMID 30342537. {{cite journal}}: Vancouver style error: initials in name 1 (help)CS1 maint: unflagged free DOI (link)
  19. ^ Chong HC, Tan CK, Huang RL, Tan NS (Feb 2012). "Matricellular proteins: a sticky affair with cancers". J. Oncol. 2012: 351089. doi:10.1155/2012/351089. PMC 3306981. PMID 22481923.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Lam CR, Yau YH, Tan CK, Huang RL, Tan SM, Tang MB, Ding JL, Kersten S, Tan NS (2010). "Angiopoietin-like 4 interacts with integrins beta1 and beta5 to modulate keratinocyte migration". Am J Pathol. 177 (6): 2791–2803. doi:10.2353/ajpath.2010.100129. PMC 2993291. PMID 20952587.
  21. ^ Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Tan CK, Huang RL, Sze SK, Tang MB, Ding JL, Kersten S, Tan NS (2010). "Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing". J Biol Chem. 285 (43): 32999–33009. doi:10.1074/jbc.M110.108175. PMC 2963335. PMID 20729546.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Chong HC, Chan JS, Goh CQ, Gounko NV, Luo B, Wang X, Foo S, Wong MT, Choong C, Kersten S, Tan NS (2014). "Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice". Mol. Ther. 22 (9): 1593–1604. doi:10.1038/mt.2014.102. PMC 4435481. PMID 24903577.
  23. ^ Teo Z, Chan J, Chong HC, Sng MK, Choo CC, Phua G, Teo D, Zhu P, Choong C, Wong M, Tan NS (2017). "Angiopoietin-like 4 induces a β-catenin-mediated upregulation of ID3 in fibroblasts to reduce scar collagen expression". Sci. Rep. 7 (1): 6303. doi:10.1038/s41598-017-05869-x. PMC 5524754. PMID 28740178. {{cite journal}}: Vancouver style error: initials in name 2 (help)
  24. ^ Chen H, Lui YS, Tan ZW, Lee J, Tan NS, Tan LP (2019). "Migration and Phenotype Control of Human Dermal Fibroblasts by Electrospun Fibrous Substrates". Adv Healthc Mater. 8 (9): e1801378. doi:10.1002/adhm.201801378. PMID 30901162. {{cite journal}}: Vancouver style error: initials in name 4 (help)
  25. ^ Mousavizadeh R, Scott A, Lu A, Ardekani GS, Behzad H, Lundgreen K, Ghaffari M, McCormack RG, Duronio V (2015). "Angiopoietin-like 4 (ANGPTL4) promotes angiogenesis in tendon and is increased in cyclically loaded tendon fibroblasts". J. Physiol. 594 (11): 2971–83. doi:10.1113/JP271752. PMC 4887665. PMID 26670924.
  26. ^ Babapoor-Farrokhran S, Jee K, Puchner B, Hassan SJ, Xin X, Rodrigues M, Kashiwabuchi F, Ma T, Hu K, Deshpande M, Daoud Y, Solomon S, Wenick A, Lutty GA, Semenza GL, Montaner S, Sodhi A (2015). "Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy". Proc Natl Acad Sci U S A. 112 (23): E3030–9. doi:10.1073/pnas.1423765112. PMC 4466723. PMID 26039997.
  27. ^ Sukonina V, Lookene A, Olivecrona T, Olivecrona G (2006). "Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue". Proc. Natl. Acad. Sci. U.S.A. 103 (46): 17450–5. doi:10.1073/pnas.0604026103. PMC 1859949. PMID 17088546.
  28. ^ Lafferty MJ, Bradford KC, Erie DA, Neher SB (Jul 2013). "Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation". J. Biol. Chem. 288 (40): 28524–34. doi:10.1074/jbc.M113.497602. PMC 3789953. PMID 23960078.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  29. ^ Georgiadi A, Wang Y, Stienstra R, Tjeerdema N, Janssen A, Stalenhoef A, van der Vliet JA, de Roos A, Tamsma JT, Smit JW, Tan NS, Müller M, Kersten S (Oct 2013). "Overexpression of Angiopoietin-like Protein 4 Protects Against Atherosclerosis". Arterioscler. Thromb. Vasc. Biol. 33 (7): 1529–37. doi:10.1161/ATVBAHA.113.301698. PMID 23640487.
  30. ^ Georgiadi A, Lichtenstein L, Degenhardt T, Boekschoten MV, van Bilsen M, Desvergne B, Müller M, Kersten S (2010). "Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and protects against fatty acid-induced oxidative stress". Circ. Res. 106 (11): 1712–1721. doi:10.1161/CIRCRESAHA.110.217380. PMID 20378851.
  31. ^ Catoire M, Alex S, Paraskevopulos N, Mattijssen F, Evers-van Gogh I, Schaart G, Jeppesen J, Kneppers A, Mensink M, Voshol PJ, Olivecrona G, Tan NS, Hesselink MK, Berbée JF, Rensen PC, Kalkhoven E, Schrauwen P, Kersten S (2014). "Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise". Proc Natl Acad Sci U S A. 111 (11): E1043–52. doi:10.1073/pnas.1400889111. PMC 3964070. PMID 24591600.
  32. ^ Xiao YL, Kash JC, Beres SB, Sheng ZM, Musser JM, Taubenberger JK (Mar 2013). "High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded autopsy lung tissue sample from the 1918 influenza pandemic". J. Pathol. 229 (4): 535–45. doi:10.1002/path.4145. PMC 3731037. PMID 23180419.
  33. ^ Li L, Chong HC, Ng SY, Kwok KW, Teo Z, Tan EH, Choo CC, Seet JE, Choi HW, Buist ML, Chow VT, Tan NS (2015). "Angiopoietin-like 4 Increases Pulmonary Tissue Leakiness and Damage during Influenza Pneumonia". Cell Rep. 10 (5): 654–663. doi:10.1016/j.celrep.2015.01.011. PMID 25660016.
  34. ^ Li L, Foo B, Kwok KW, Sakamoto N, Mukae H, Izumikawa K, Mandard S, Quenot JP, Lagrost L, Teh WK, Singh Kohli G, Zhu P, Choi H, Buist ML, Seet JE, Yang L, He F, Kwong Chow VT, Tan NS (2019). "Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia". mBio. 10 (3): pii: e02469-18. doi:10.1128/mBio.02469-18. PMID 31164474. {{cite journal}}: Vancouver style error: initials in name 2 (help)

External links

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=ANGPTL4&oldid=902396828"