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Allograft inflammatory factor 1

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AIF1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAIF1, AIF-1, IBA1, IRT-1, IRT1, allograft inflammatory factor 1, Iba-1
External IDsOMIM: 601833; MGI: 1343098; HomoloGene: 1226; GeneCards: AIF1; OMA:AIF1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

199

11629

Ensembl

ENSMUSG00000024397

UniProt

P55008
Q4V347

O70200

RefSeq (mRNA)

NM_001623
NM_004847
NM_032955
NM_001318970

NM_019467
NM_001361501
NM_001361502

RefSeq (protein)

NP_001305899
NP_001614
NP_116573
NP_001614.3

NP_062340
NP_001348430
NP_001348431

Location (UCSC)Chr 6: 31.62 – 31.62 MbChr 17: 35.39 – 35.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Allograft inflammatory factor 1 (AIF-1) also known as ionized calcium-binding adapter molecule 1 (IBA1) is a protein that in humans is encoded by the AIF1 gene.[5][6]

Gene

The AIF1 gene is located within a segment of the major histocompatibility complex class III region. It has been shown that this gene is highly expressed in testis and spleen, but weakly expressed in brain, lung, and kidney. Among brain cells, the Iba1 gene was specifically expressed in microglia. Upon activation of microglia due to inflammation, expression of Iba1 is upregulated allowing the discrimination between surveiling and activated microglia.

Function

AIF1 is a protein that exists in the cytoplasm, and it is highly evolutionarily conserved. It is also possibly identical to three other proteins, Iba-1, MRF-1 (microglia response factor) and daintain. However complete functional profiles of all three proteins and how they overlap is unknown.[7] IBA1 is a 17-kDa EF hand protein that is specifically expressed in macrophages / microglia and is upregulated during the activation of these cells. Iba1 expression is up-regulated in microglia following nerve injury,[8] central nervous system ischemia, and several other brain diseases.

AIF1 was originally discovered in atherosclerotic lesions in a rat model of chronic allograft cardiac rejection. It was found to be upregulated in macrophages and neutrophils in response to the cytokine IFN-γ.[9] AIF1 expression has been seen to increase in vascular tissue in response to arterial injury, specifically it is found in activated vascular smooth muscle cells in response to IFN-γ, IL-1β, and T-cell conditioned media.[10] In vascular smooth muscle cells, activation is responsible for arterial thickening in allografts through over proliferation. AIF1 has been found to enhance growth and promote proliferation in vascular smooth muscle cells through deregulation of the cell cycle. It does this by shortening the cell cycle and altering the expression of cyclins.[11] Though histologically different, AIF1 has also been shown to promote the proliferation and activation of endothelial cells (EC). EC activation, leads to proliferation and migration of cells, which is involved in multiple normal vascular processes, such as atherosclerosis, angiogenesis, and wound healing. It is currently theorized that AIF1 works to control endothelial cell proliferation and migration through action in signal transduction pathways.[12] It has features of a cytoplasmic signaling protein, including several domains that allow for binding to multiprotein complexes, called PDZ domains.[13] In endothelial cells, AIF1 has been specifically shown to regulate vasculogenesis, including the formation of aortic sprouting and tube-like formations. AIF1 been shown to interact with kinase p44/42 and PAK1, two previously known signal transduction molecules, in regulating these processes. AIF1 also shows distinct differences in the pathways by which it regulates endothelial cells, macrophages, and vascular smooth muscle cells.[12]

Clinical significance

Allograft Inflammatory Factor 1 is found in activated macrophages. Activated macrophages are found in tissues with inflammation. AIF1 levels in healthy humans have been found to positively correlate with metabolic indicators, such as body mass index, triglycerides, and fasting plasma glucose levels. The excess of adipose tissue found in obese patients is found to cause chronic inflammation with an increase in the number of activated macrophages. Subsequently, AIF1 may be an accurate indicator of macrophage activation in the body.[14] There is also evidence that AIF1 could be a diabetic nephropathy when detected in serum.[15] Since diabetic nephropathy is a consequence of long-term type 1 and type 2 diabetes, this consistent with evidence that AIF1 may be associated with other aspects of diabetes. It is found in activated macrophages in the pancreatic islets, and has been shown to decrease insulin secretion, while simultaneously impairing glucose elimination.[16]

References

  1. ^ a b c ENSG00000235985, ENSG00000235588, ENSG00000234836, ENSG00000237727, ENSG00000204472 GRCh38: Ensembl release 89: ENSG00000206428, ENSG00000235985, ENSG00000235588, ENSG00000234836, ENSG00000237727, ENSG00000204472 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024397 – 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. ^ Autieri MV (Dec 1996). "cDNA cloning of human allograft inflammatory factor-1: tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries". Biochem Biophys Res Commun. 228 (1): 29–37. doi:10.1006/bbrc.1996.1612. PMID 8912632.
  6. ^ "Entrez Gene: AIF1 allograft inflammatory factor 1".
  7. ^ Deininger MH, Meyermann R, Schluesener HJ (March 2002). "The allograft inflammatory factor-1 family of proteins". FEBS Lett. 514 (2–3): 115–21. doi:10.1016/S0014-5793(02)02430-4. PMID 11943136.
  8. ^ Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S (June 1998). "Microglia-specific localisation of a novel calcium binding protein, Iba1". Brain Res. Mol. Brain Res. 57 (1): 1–9. doi:10.1016/s0169-328x(98)00040-0. PMID 9630473.
  9. ^ Utans U, Arceci RJ, Yamashita Y, Russell ME (June 1995). "Cloning and characterization of allograft inflammatory factor-1: a novel macrophage factor identified in rat cardiac allografts with chronic rejection". J. Clin. Invest. 95 (6): 2954–62. doi:10.1172/JCI118003. PMC 295984. PMID 7769138.
  10. ^ Autieri MV, Carbone C, Mu A (July 2000). "Expression of allograft inflammatory factor-1 is a marker of activated human vascular smooth muscle cells and arterial injury". Arterioscler. Thromb. Vasc. Biol. 20 (7): 1737–44. doi:10.1161/01.ATV.20.7.1737. PMID 10894811.
  11. ^ Autieri MV, Carbone CM (September 2001). "Overexpression of allograft inflammatory factor-1 promotes proliferation of vascular smooth muscle cells by cell cycle deregulation". Arterioscler. Thromb. Vasc. Biol. 21 (9): 1421–6. doi:10.1161/hq0901.095566. PMID 11557666.
  12. ^ a b Tian Y, Jain S, Kelemen SE, Autieri MV (February 2009). "AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis". Am. J. Physiol., Cell Physiol. 296 (2): C256–66. doi:10.1152/ajpcell.00325.2008. PMC 2643850. PMID 18787073.
  13. ^ Hung AY, Sheng M (February 2002). "PDZ domains: structural modules for protein complex assembly". J. Biol. Chem. 277 (8): 5699–702. doi:10.1074/jbc.R100065200. PMID 11741967.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  14. ^ Fukui M, Tanaka M, Toda H, Asano M, Yamazaki M, Hasegawa G, Imai S, Fujinami A, Ohta M, Nakamura N (July 2012). "The serum concentration of allograft inflammatory factor-1 is correlated with metabolic parameters in healthy subjects". Metab. Clin. Exp. 61 (7): 1021–5. doi:10.1016/j.metabol.2011.12.001. PMID 22225958.
  15. ^ Fukui M, Tanaka M, Asano M, Yamazaki M, Hasegawa G, Imai S, Fujinami A, Ohta M, Obayashi H, Nakamura N (July 2012). "Serum allograft inflammatory factor-1 is a novel marker for diabetic nephropathy". Diabetes Res. Clin. Pract. 97 (1): 146–50. doi:10.1016/j.diabres.2012.04.009. PMID 22560794.
  16. ^ Chen ZW, Ahren B, Ostenson CG, Cintra A, Bergman T, Möller C, Fuxe K, Mutt V, Jörnvall H, Efendic S (December 1997). "Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats". Proc. Natl. Acad. Sci. U.S.A. 94 (25): 13879–84. doi:10.1073/pnas.94.25.13879. PMC 28401. PMID 9391121.

Further reading

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