FGF15

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Fibroblast growth factor 15
Identifiers
OrganismMus musculus
SymbolFgf15
Entrez14170
HomoloGene3754
RefSeq (mRNA)NM_008003.2
RefSeq (Prot)NP_032029.1
UniProtO35622
Other data
Chromosome7: 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

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

Structure

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

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

  1. ^ NCBI. "Mouse FGF15 fibroblast growth factor 15".
  2. ^ Jones SA (2012). Physiology of FGF15/19. Advances in Experimental Medicine and Biology. Vol. 728. pp. 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. 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. 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, Luo G, Jones SA, Goodwin B, Richardson JA, Gerard RD, Repa JJ, Mangelsdorf DJ, Kliewer SA (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, Moschetta A (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, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ (Mar 2011). "FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis". Science. 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, Lin M, Forman BM, Huang W (Dec 2012). "Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice". Hepatology. 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, Aleksunes LM, Richardson JR, Apte U, Rudnick DA, Guo GL (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. PMC 4024724. PMID 24699334.