| Literature DB >> 25108224 |
Keiko Sakai1, Safdar Jawaid2, Takako Sasaki3, George Bou-Gharios4, Takao Sakai5.
Abstract
We previously identified transforming growth factor (TGF)-β signaling as a fibronectin-independent mechanism of type I collagen fibrillogenesis following adult liver injury. To address the contribution of TGF-β signaling during the development of liver fibrosis, we generated adult mice lacking TGF-β type II receptor (TGF-βIIR) from the liver. TGF-βIIR knockout livers indeed showed a dominant effect in reducing fibrosis, but fibrosis still remained approximately 45% compared with control and fibronectin knockout livers. Unexpectedly, this was accompanied by significant up-regulation of connective tissue growth factor mRNA levels. Organized type I collagen networks in TGF-βIIR knockout livers colocalized well with fibronectin. We provide evidence that elimination of TGF-βIIR is not sufficient to completely prevent liver fibrosis. Our results indicate a TGF-β-independent mechanism of type I collagen production and suggest connective tissue growth factor as its potent mediator. We advocate combined elimination of TGF-β signaling and connective tissue growth factor as a potential therapeutic target by which to attenuate liver fibrosis.Entities:
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Year: 2014 PMID： 25108224 PMCID： PMC4715221 DOI： 10.1016/j.ajpath.2014.06.009
Source DB: PubMed Journal: Am J Pathol ISSN： 0002-9440 Impact factor: 4.307