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Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways

Pengfei Xu1, Yingjie Zhang1, Yunye Liu1

  • 1Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin, PR China.

Toxicology and Applied Pharmacology
|November 24, 2015
PubMed

Insights

Fibroblast growth factor 21 (FGF-21) shows promise in treating liver fibrosis. This study found FGF-21 effectively reduced liver fibrosis in mice by inhibiting hepatic stellate cell activation and promoting apoptosis.

Area of Science:

  • Hepatology and Molecular Biology
  • Endocrinology

Background:

  • Fibroblast growth factor 21 (FGF-21) is known for its anti-diabetic and lipocaic effects.
  • The protective role of FGF-21 against hepatic fibrosis remains uninvestigated.

Purpose of the Study:

  • To investigate the efficacy of FGF-21 in attenuating dimethylnitrosamine (DMN)-induced hepatic fibrosis in a mouse model.
  • To elucidate the underlying mechanisms by which FGF-21 exerts its antifibrotic effects.

Main Methods:

  • Hepatic fibrosis was induced using DMN injections in mice, with concurrent daily administration of FGF-21.
  • Assessment of fibrosis involved histopathology, 4-hydroxyproline content, and expression of α-SMA and collagen I.
  • Mechanisms were explored using activated hepatic stellate cells (HSCs) treated with ethanol/PDGF-BB.

Main Results:

  • FGF-21 treatment significantly attenuated hepatic fibrogenesis, reducing fibrosis markers like 4-hydroxyproline, α-SMA, and collagen I.
  • FGF-21 inhibited HSC activation by downregulating TGF-β, NF-κB nuclear translocation, and smad2/3 and IκBα phosphorylation.
  • FGF-21 induced apoptosis in activated HSCs, evidenced by increased Caspase-3 and altered Bcl-2/Bax ratio.

Conclusions:

  • FGF-21 demonstrates significant antifibrotic effects in a DMN-induced mouse model.
  • FGF-21 inhibits hepatic stellate cell activation and promotes their apoptosis, key mechanisms in reducing liver fibrosis.
  • FGF-21 represents a potential therapeutic agent for treating hepatic fibrosis.
Keywords:
Fibroblast growth factor 21Hepatic fibrogenesisHepatic stellate cellsNF-κBTGF-β

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