Hepatocyte growth factor suppresses transforming growth factor-beta-1 and type III collagen in human primary renal

Shan Mou1, Qin Wang, Beili Shi

  • 1Renal Division, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Insights

Hepatocyte growth factor (HGF) may prevent diabetic kidney fibrosis by inhibiting transforming growth factor-beta-1 (TGF-beta1) signaling. HGF administration could be a novel therapeutic approach for diabetic nephropathy.

Area of Science:

  • Nephrology
  • Cell Biology
  • Molecular Medicine

Background:

  • Diabetic kidney disease is characterized by tubulointerstitial changes and renal fibrosis.
  • Transforming growth factor-beta-1 (TGF-beta1) is implicated in diabetic kidney fibrosis.
  • Hepatocyte growth factor (HGF) has demonstrated therapeutic potential in animal models of kidney injury.

Purpose of the Study:

  • To investigate if HGF's preventive effects on diabetic kidney fibrosis involve modulating TGF-beta1 signaling and collagen III secretion.
  • To examine the expression dynamics of HGF/c-Met and TGF-beta1 in renal fibroblasts under high-glucose conditions.
  • To determine the impact of recombinant human HGF on TGF-beta1 expression and collagen III production.

Main Methods:

  • Cultured human renal fibroblasts under high-glucose conditions.
  • Assessed HGF, c-Met, and TGF-beta1 expression using RT-PCR and Western blotting.
  • Quantified collagen III levels via ELISA.
  • Administered recombinant human HGF to evaluate dose-dependent effects.

Main Results:

  • HGF and c-Met expression were detected in renal fibroblasts within 6 hours of high-glucose exposure.
  • TGF-beta1 levels peaked at 96 hours under high-glucose conditions.
  • Recombinant human HGF significantly inhibited TGF-beta1 mRNA expression and reduced collagen III secretion by 34% in a dose-dependent manner.

Conclusions:

  • HGF inhibits TGF-beta1 signaling and type III collagen activation in renal fibroblasts during hyperglycemia.
  • The balance between HGF and TGF-beta1 is crucial in the pathogenesis of chronic renal fibrosis.
  • HGF administration represents a potential therapeutic strategy for managing renal fibrogenesis in diabetic nephropathy.

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