FGF15

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Fibroblast growth factor 15
Identifiers
Organism Mus musculus
Symbol Fgf15
Entrez 14170
HomoloGene 3754
RefSeq (mRNA) NM_008003.2
RefSeq (Prot) NP_032029.1
UniProt O35622
Other data
Chromosome 7: 144.9 - 144.9 Mb

Fibroblast growth factor 15 is a protein in mouse encoded by the Fgf15 gene.[1] It is a member of the fibroblast growth factor (FGF) family but, like FGF19, FGF21 and FGF23, has endocrine functions. FGF19 is the orthologous protein in humans. They are often referred together as FGF15/19.[2][3]

Identification[edit]

FGF15 was first described in developing mouse brain.[4][5][6] There is no human FGF15.

Structure[edit]

The mouse Fgf15 gene is syntenic with the human FGF19 gene.[7] FGF15 and FGF19 proteins share about 50% amino acid identity, are found in the same tissues, and have similar functions in mouse and humans.

Functions[edit]

FGF15 is found in the absorptive cells of the mouse ileum and plays an important role in feedback inhibition of hepatic bile acid synthesis.[8] FGF15 (and FGF19 in humans) function as hormones produced in response to bile acid absorption acting on the farnesoid X receptor FXR, are secreted into the portal venous circulation and bind onto the liver membrane receptor FGFR4/β-Klotho and repress bile acid synthesis by the Cyp7a1 gene.

In a mouse model of chronic diarrhea due to bile acid malabsorption, FGF15 administration, or stimulation of its production, reduced the bile acid loss by inhibiting new synthesis.[9]

FGF15 has effects on energy homeostasis. Fgf15-knock-out mice have reduced liver glycogen storage and are glucose-intolerant.[10]

FGF15 has been implicated in liver regeneration and repair.[11] Fgf15-deficient mice have impaired regeneration.[12]

References[edit]

  1. ^ NCBI. "Mouse FGF15 fibroblast growth factor 15". 
  2. ^ Jones SA (2012). "Physiology of FGF15/19". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology 728: 171–82. doi:10.1007/978-1-4614-0887-1_11. ISBN 9781461408871. PMID 22396169. 
  3. ^ Potthoff MJ, Kliewer SA, Mangelsdorf DJ (Feb 2012). "Endocrine fibroblast growth factors 15/19 and 21: from feast to famine". Genes & Development 26 (4): 312–324. doi:10.1101/gad.184788.111. PMC 3289879. PMID 22302876. 
  4. ^ McWhirter JR, Goulding M, Weiner JA, Chun J, Murre C (Sep 1997). "A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1". Development (Cambridge, England) 124 (17): 3221–32. PMID 9310317. 
  5. ^ Gimeno L, Hashemi R, Brûlet P, Martínez S (2002). "Analysis of Fgf15 expression pattern in the mouse neural tube". Brain Research Bulletin 57 (3-4): 297–9. doi:10.1016/S0361-9230(01)00717-1. PMID 11922976. 
  6. ^ Gimeno L, Brûlet P, Martínez S (Aug 2003). "Study of Fgf15 gene expression in developing mouse brain". Gene Expression Patterns : GEP 3 (4): 473–81. doi:10.1016/S1567-133X(03)00059-0. PMID 12915315. 
  7. ^ Wright TJ, Ladher R, McWhirter J, Murre C, Schoenwolf GC, Mansour SL (May 2004). "Mouse FGF15 is the ortholog of human and chick FGF19, but is not uniquely required for otic induction". Developmental Biology 269 (1): 264–75. doi:10.1016/j.ydbio.2004.02.003. PMID 15081372. 
  8. ^ Inagaki T, Choi M, Moschetta A, Peng L, Cummins CL, McDonald JG et al. (Oct 2005). "Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis". Cell Metabolism 2 (4): 217–25. doi:10.1016/j.cmet.2005.09.001. PMID 16213224. 
  9. ^ Jung D, Inagaki T, Gerard RD, Dawson PA, Kliewer SA, Mangelsdorf DJ et al. (Dec 2007). "FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption". Journal of Lipid Research 48 (12): 2693–700. doi:10.1194/jlr.M700351-JLR200. PMID 17823457. 
  10. ^ Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K et al. (Mar 2011). "FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis". Science (New York, N.Y.) 331 (6024): 1621–4. doi:10.1126/science.1198363. PMC 3076083. PMID 21436455. 
  11. ^ Zhang L, Wang YD, Chen WD, Wang X, Lou G, Liu N et al. (Dec 2012). "Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice". Hepatology (Baltimore, Md.) 56 (6): 2336–43. doi:10.1002/hep.25905. PMC 3477501. PMID 22711662. 
  12. ^ Kong B, Huang J, Zhu Y, Li G, Williams J, Shen S et al. (May 2014). "Fibroblast growth factor 15 deficiency impairs liver regeneration in mice". American Journal of Physiology. Gastrointestinal and Liver Physiology 306 (10): G893–902. doi:10.1152/ajpgi.00337.2013. PMID 24699334.