title: Low-molecular-weight fibroblast growth factor 2 attenuates hepatic fibrosis by epigenetic down-regulation of Delta-like1.
abstract: Liver fibrosis, a major cause of end-stage liver diseases, is closely regulated by multiple growth factors and cytokines. The correlation of fibroblast growth factor 2 (FGF2) with chronic liver injury has been reported, but the exact functions of different FGF2 isoforms in liver fibrogenesis remain unclear. Here, we report on the differential expression patterns and functions of low- and high-molecular-weight FGF2 (namely, FGF2(lmw) and FGF2(hmw) , respectively) in hepatic fibrogenesis using a CCl4 -induced mouse liver fibrosis model. FGF2(hmw) displayed a robust increase in CCl4 -induced hepatic fibrosis and promoted fibrogenesis. In contrast, endogenous FGF2(lmw) exhibited a slight increase in hepatic fibrosis and suppressed this pathological progression. Moreover, exogenous administration of recombinant FGF2(lmw) potently ameliorated CCl4 -induced liver fibrosis. Mechanistically, we showed that FGF2(lmw) treatment attenuated hepatic stellate cell activation and fibrosis by epigenetic down-regulation of Delta-like 1 expression through the p38 mitogen-activated protein kinase pathway.
  
  
  CONCLUSIONS
  FGF2(lmw) and FGF2(hmw) have distinct roles in liver fibrogenesis. These findings demonstrate a potent antifibrotic effect of FGF2(lmw) administration, which may provide a novel approach to treat chronic liver diseases.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Ruo-Lang
authors.initials: RL
authors.lastname: Pan
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Xiang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.forename: Wendong
authors.initials: W
authors.lastname: Huang
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Shao
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2