| First Author | Sakai K | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 10 | Pages | 2611-7 |
| PubMed ID | 25108224 | Mgi Jnum | J:214834 |
| Mgi Id | MGI:5604060 | Doi | 10.1016/j.ajpath.2014.06.009 |
| Citation | Sakai K, et al. (2014) Transforming growth factor-beta-independent role of connective tissue growth factor in the development of liver fibrosis. Am J Pathol 184(10):2611-7 |
| abstractText | We previously identified transforming growth factor (TGF)-beta signaling as a fibronectin-independent mechanism of type I collagen fibrillogenesis following adult liver injury. To address the contribution of TGF-beta signaling during the development of liver fibrosis, we generated adult mice lacking TGF-beta type II receptor (TGF-betaIIR) from the liver. TGF-betaIIR 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-betaIIR knockout livers colocalized well with fibronectin. We provide evidence that elimination of TGF-betaIIR is not sufficient to completely prevent liver fibrosis. Our results indicate a TGF-beta-independent mechanism of type I collagen production and suggest connective tissue growth factor as its potent mediator. We advocate combined elimination of TGF-beta signaling and connective tissue growth factor as a potential therapeutic target by which to attenuate liver fibrosis. |
