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Updated: Nov 11, 2025

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

11.5K

The MSP-RON pathway regulates liver fibrosis through transforming growth factor beta-dependent epithelial-mesenchymal

Tianhao Weng1, Dong Yan1, Danrong Shi1

  • 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Liver International : Official Journal of the International Association for the Study of the Liver
|March 31, 2021
PubMed
Abstract

Insights

Macrophage-stimulating protein (MSP) is elevated in liver cirrhosis and drives fibrosis by promoting hepatocyte epithelial-mesenchymal transition (EMT). Targeting the MSP-RON pathway offers a novel therapeutic strategy for liver cirrhosis.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Fibrosis Research

Background:

  • Liver fibrosis is a critical step in cirrhosis development.
  • Epithelial-mesenchymal transition (EMT) is a key process in organ fibrosis.
  • The role of the Macrophage-stimulating protein (MSP)-RON pathway in liver fibrosis was previously unclear.

Purpose of the Study:

  • To elucidate the biological profile and mechanisms of the MSP-RON pathway in liver fibrosis.
  • To identify the MSP-RON pathway as a potential therapeutic target for liver cirrhosis.

Main Methods:

  • Evaluated MSP expression in 57 cirrhosis cases and controls.
  • Assessed MSP-RON pathway effects on liver fibrosis in vitro and in vivo.
  • Tested therapeutic efficacy of MSP or RON inhibition in a mouse liver fibrosis model.

Main Results:

  • MSP was upregulated in liver cirrhosis, correlating with poor prognosis.
  • The MSP-RON pathway promoted hepatocyte EMT, dependent on the TGF-β pathway.
  • MSP blocking antibody and RON inhibitor BMS-777607 reduced liver fibrosis in mice.

Conclusions:

  • MSP serves as a prognostic biomarker for liver cirrhosis.
  • The MSP-RON pathway exacerbates liver fibrosis via TGF-β-dependent EMT.
  • Targeted inhibition of MSP/RON presents a new therapeutic avenue for liver cirrhosis.
Keywords:
RON receptor tyrosine kinaseepithelialliver fibrosismacrophage-stimulating proteinmesenchymal transitiontransforming growth factor-beta

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