title: Hepatocyte-derived Snail1 propagates liver fibrosis progression.
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.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: R Grant
authors.initials: RG
authors.lastname: Rowe
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Lin
authors.forename: Ryoko
authors.initials: R
authors.lastname: Shimizu-Hirota
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hanada
authors.forename: Eric G
authors.initials: EG
authors.lastname: Neilson
authors.forename: Joel K
authors.initials: JK
authors.lastname: Greenson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D008103:Liver Cirrhosis / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors