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Down‐regulation of Smurf1 and Smurf2 is involved in the Initiation and Progression of Hepatic Fibrotic rats
Author(s) -
ZHANG GUO,
PENG PENG,
CHEN LI,
CHEN XINZHOU,
ZHANG FACAN
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1018.13
Subject(s) - hepatic stellate cell , hepatic fibrosis , desmin , smad , chemistry , immunohistochemistry , fibrosis , alpha (finance) , endocrinology , western blot , medicine , downregulation and upregulation , cancer research , biology , microbiology and biotechnology , transforming growth factor , vimentin , biochemistry , gene , construct validity , nursing , patient satisfaction
The detail mechanisms undergoing degradation of TGFbeta/Smad molecules are poorly understood. This study was designed to determine if novel Smurfs‐dependent degradation machinery is involved in the hepatic fibrosis. Rats with hepatic fibrosis were induced by 40% carbon tetrachloride. Immunohistochemistry staining and western blot were performed to quantify the expression levels of Smurf1 and Smurf 2 in normal and fibrotic liver tissues. In parallel, the hepatic stellate cells (HSCs) marker Desmin and alpha‐SMA were dynamically measured as well. Furthermore, in vitro study was performed to elucidate the relationship among Smad3, Smad7, alpha (2) I collagen and Smurf1&2 levels in cultured HSCs by using specific siRNA to block the Smurf1&2 mRNA. It was found that either Smurf1 or Smurf2 was enriched in normal hepatic Disse space. However, the expression levels of alpha‐SMA but not Desmin, Smurf1 or Smurf2 have significantly increased in fibrotic rats (P<0.01). In those rats with hepatic fibrosis, both Smurf1 and Smurf2, particular Smurf2, were found to markedly decrease (P<0.01). Both decrement of Smurf1 and Smurf2 are associated to the increasing levels in phosphorylation of Smad3 as well as alpha (2) I collagen mRNA in these cells. Our data indicate that down‐regulation of Smurf1&2 in liver may importantly initialize and participate in the process of hepatic fibrosis. (Supported by NSFC 30960145 and GHF 200958, zhangfacan@126.com )