Hepatocyte-derived snail1 propagates liver fibrosis progression

R. Grant Rowe, Yongshun Lin, Ryoko Shimizu-Hirota, Shinichiro Hanada, Eric G. Neilson, Joel K. Greenson, Stephen J. Weiss

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Chronic exposure of the liver to hepatotoxic agents initiates an aberrant wound healing response marked by proinflammatory, as well as fibrotic, changes, leading to compromised organ structure and function. In a variety of pathological states, correlative links have been established between tissue fibrosis and the expression of transcription factors associated with the induction of epithelial-mesenchymal cell transition (EMT) programs similar to those engaged during development. However, the role played by endogenously derived, EMT-associated transcription factors in fibrotic states in vivo remains undefined. Using a mouse model of acute liver fibrosis, we demonstrate that hepatocytes upregulate the expression of the zinc finger transcriptional repressor, Snail1, during tissue remodeling. Hepatocyte-specific ablation of Snail1 demonstrates that this transcription factor plays a key role in liver fibrosis progression in vivo by triggering the proximal genetic programs that control multiple aspects of fibrogenesis, ranging from growth factor expression and extracellular matrix biosynthesis to the ensuing chronic inflammatory responses that characterize this class of pathological disorders.

Original languageEnglish
Pages (from-to)2392-2403
Number of pages12
JournalMolecular and cellular biology
Volume31
Issue number12
DOIs
Publication statusPublished - 2011 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Rowe, R. G., Lin, Y., Shimizu-Hirota, R., Hanada, S., Neilson, E. G., Greenson, J. K., & Weiss, S. J. (2011). Hepatocyte-derived snail1 propagates liver fibrosis progression. Molecular and cellular biology, 31(12), 2392-2403. https://doi.org/10.1128/MCB.01218-10