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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-31
pubmed:abstractText
Following liver injury, the wound-healing process is characterized by hepatic stellate cell (HSC) activation from the quiescent fat-storing phenotype to a highly proliferative myofibroblast-like phenotype. Snail1 is a transcription factor best known for its ability to trigger epithelial-mesenchymal transition, to influence mesoderm formation during embryonic development, and to favor cell survival. In this study, we evaluated the expression of Snail1 in experimental and human liver fibrosis and analyzed its role in the HSC transdifferentiation process. Liver samples from patients with liver fibrosis and from mice treated by either carbon tetrachloride (CCl(4)) or thioacetamide (TAA) were evaluated for mRNA expression of Snail1. The transcription factor expression was investigated by immunostaining and real-time quantitative RT-PCR (qRT-PCR) on in vitro and in vivo activated murine HSC. Snail1 knockdown studies on cultured HSC and on CCl(4)-treated mice were performed by adenoviral delivery of short-hairpin RNA; activation-related genes were quantitated by real-time qRT-PCR and Western blotting. Snail1 mRNA expression resulted upregulated in murine experimental models of liver injury and in human hepatic fibrosis. In vitro studies showed that Snail1 is expressed by HSC and that its transcription is augmented in in vitro and in vivo activated HSC compared with quiescent HSC. At the protein level, we could observe the nuclear translocation of Snail1 in activated HSC. Snail1 knockdown resulted in the downregulation of activation-related genes both in vitro and in vivo. Our data support a role for Snail1 transcription factor in the hepatic wound-healing response and its involvement in the HSC transdifferentiation process.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1522-1547
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G316-26
pubmed:meshHeading
pubmed-meshheading:21088236-Acute Disease, pubmed-meshheading:21088236-Adult, pubmed-meshheading:21088236-Aged, pubmed-meshheading:21088236-Animals, pubmed-meshheading:21088236-Blotting, Western, pubmed-meshheading:21088236-Carbon Tetrachloride, pubmed-meshheading:21088236-Cell Transdifferentiation, pubmed-meshheading:21088236-Cells, Cultured, pubmed-meshheading:21088236-Chronic Disease, pubmed-meshheading:21088236-Gene Silencing, pubmed-meshheading:21088236-Hepatic Stellate Cells, pubmed-meshheading:21088236-Humans, pubmed-meshheading:21088236-Immunologic Techniques, pubmed-meshheading:21088236-Liver, pubmed-meshheading:21088236-Liver Cirrhosis, pubmed-meshheading:21088236-Mice, pubmed-meshheading:21088236-Middle Aged, pubmed-meshheading:21088236-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21088236-Thioacetamide, pubmed-meshheading:21088236-Transcription Factors, pubmed-meshheading:21088236-Up-Regulation, pubmed-meshheading:21088236-Wound Healing
pubmed:year
2011
pubmed:articleTitle
Snail1 transcription factor is a critical mediator of hepatic stellate cell activation following hepatic injury.
pubmed:affiliation
University of Padova, School of Pharmacy, Dept. of Histology, Microbiology and Medical Biotechnologies, Via A. Gabelli 63, 35121 Padova, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't