Table 1.

Regulation of HSCs and development of hepatic fibrosis by various FGF isoforms.

FGF subfamily	Study	Findings
FGF1 subfamily	Lin et al. [16]	FGF2 induces collagen 1α1 and αSMA in HSCs in vitro. FGF2 increases HSC proliferation mediated by MEK/ERK signaling.
FGF1 subfamily	Nakamura et al. [20]	FGF2 increases proliferation of Lx-2 cells. Inhibition of FGFR1 does not alter αSMA induction in Lx-2 cells treated with TGFβ.
FGF1 subfamily	Yu et al. [22]	Single and double knockout of FGF1 and FGF2 decreases CCl4 induced hepatic fibrosis. Single and double FGF1 and FGF2 knockout mice have reduced collagen 1α1 expression but not αSMA. Desmin expression in the liver remained constant in FGF1 and FGF2 deficient mice indicating FGF1 and FGF2 do not affect HSC proliferation.
FGF1 subfamily	Antoine et al. [13]	FGF2 treatment fails to affect the proliferation of Lx-2 cells or primary rat HSCs in vitro.
FGF1 subfamily	Rosenbaum et al. [23]	TGFβ increases the expression of FGF2 by MFLCs. FGF2 mediates TGFβ induced HSC proliferation but does not alter expression of fibronectin.
FGF7 subfamily	Steiling et al. [26]	FGF7 is expressed in fibrotic livers but not healthy controls. FGF7 expression is colocalized with αSMA in stained liver sections.
FGF7 subfamily	Otte et al. [27]	IHC of liver sections from rats treated with phenobarbitone and CCl4 revealed FGF7 is exclusively expressed by HSCs in fibrotic foci. Severity of hepatic fibrosis correlated positively to FGF7 expression.
FGF7 subfamily	Tsai and Wang [28]	FGF7 accelerates DNA incorporation of BrdU and expression of PCNA in hepatocytes after partial hepatectomy.
FGF9 subfamily	Antoine et al. [13]	FGF9 is expressed in hepatocytes and HSCs basally but is greatly upregulated in HSCs after CCl4 exposure. FGF16 and FGF20 expression has not been detected in HSCs. FGF9 induces hepatocyte proliferation but not HSC proliferation.
FGF19 subfamily	Uriarte et al. [15]	FGF15 deficiency reduces hepatic fibrosis in mice treated with DEN and CCl4. Collagen 1α1, Timp1, αSMA, and CTGF expression induced by CCl4 is mitigated in FGF15 deficient mice. CCl4 treatment of transgenic mice overexpressing FGF15 have 3-fold higher expression of TGFβ and CTGF compared to WT mice. FGF15 signaling increases CTGF release from hepatocytes leading to the paracrine activation of HSCs.
FGF19 subfamily	Xu et al. [41]	DMN treated mice cotreated with FGF21 have had reduced fibrosis and mitigated expression of collagen 1α1, αSMA, and TGFβ. FGF21 reduced TGFβ signaling is observed as a decrease in pSmad2/3 : Smad2/3 ratio. FGF21 attenuates DMN induced hepatic inflammation and reduces TNFα, IL-6, and IL-1β expression. In vitro treatment of T6 cells with FGF21 decreases alcohol and PDGF inductions of collagen 1α1, αSMA, and TGFβ. FGF21 reduces Bcl-2/Bax ratio in vitro in cultured T6 cells.
FGF19 subfamily	Fisher et al. [42]	FGF21 deficient mice fed a MCDD have increased fibrosis with increased expression of collagen 1α1, αSMA, and TGFβ. MCDD fed FGF21 knockout mice have increased hepatic inflammation with increased expression of MCP-1, MIP1α, IL-1β, and CD36. The increased expression of profibrotic and proinflammatory genes in FGF21 deficient mice is reversible by continuous subcutaneous infusion of FGF21.