Fibroblast growth factor 15 | |||||||
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Identifiers | |||||||
Organism | |||||||
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 | ||||||
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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]
FGF15 was first described in developing mouse brain. [4] [5] [6] There is no human FGF15.
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.
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]
Klotho is an enzyme that in humans is encoded by the KL gene. The three subfamilies of klotho are α-klotho, β-klotho, and γ-klotho. α-klotho activates FGF23, and β-klotho activates FGF19 and FGF21. When the subfamily is not specified, the word "klotho" typically refers to the α-klotho subfamily, because α-klotho was discovered before the other members.
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.
The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4, is a nuclear receptor that is encoded by the NR1H4 gene in humans.
The liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized.
In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 gene.
Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.
Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 is a nuclear receptor that in humans is encoded by the RXRA gene.
Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.
Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.
UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the UGT2B4 gene.
Tumor necrosis factor receptor superfamily member 12A also known as the TWEAK receptor (TWEAKR) is a protein that in humans is encoded by the TNFRSF12A gene.
Fibroblast growth factor 19 is a protein that in humans is encoded by the FGF19 gene. It functions as a hormone, regulating bile acid synthesis, with effects on glucose and lipid metabolism. Reduced synthesis, and blood levels, may be a factor in chronic bile acid diarrhea and in certain metabolic disorders.
Fibroblast growth factor 21 is a protein that in mammals is encoded by the FGF21 gene. The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family and specifically a member of the endocrine subfamily which includes FGF23 and FGF15/19. FGF21 is the primary endogenous agonist of the FGF21 receptor, which is composed of the co-receptors FGF receptor 1 and β-Klotho.
Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective. It is recognised as a disability in the United Kingdom under the Equality Act 2010
7α-Hydroxy-4-cholesten-3-one is an intermediate in the biochemical synthesis of bile acids from cholesterol. Its precursor, 7α-hydroxycholesterol, is produced from cholesterol by hepatic cholesterol 7α-hydroxylase (CYP7A1).
FGF15/19 refers to two orthologous fibroblast growth factors which share 50% aminoacid identity and have similar functions. FGF15 was described in the mouse; FGF19 was found in humans and other species. They share physiological functions and so are often referred to as FGF15/19 or as FGF15/FGF19.
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.
Fexaramine is an investigational compound which acts as an agonist of the farnesoid X receptor (FXR), which is a bile acid-activated nuclear receptor that controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism through actions in the liver and intestine.
David Dudley Moore is an American molecular biologist known for his work investigating nuclear hormone receptors. He is a Professor and Chair of the Department of Nutritional Sciences & Toxicology at the University of California, Berkeley. He was a founding editor for the Current Protocols series of laboratory manuals in 1987.