Transforming growth Factor-β-Independent role of connective tissue growth factor in the development of liver fibrosis

Keiko Sakai, Safdar Jawaid, Takako Sasaki, George Bou-Gharios, Takao Sakai

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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- β IIR) from the liver. TGF- β IIR 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- β IIR knockout livers colocalized well with fibronectin. We provide evidence that elimination of TGF- β IIR 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.

Original languageEnglish
Pages (from-to)2611-2617
Number of pages7
JournalAmerican Journal of Pathology
Volume184
Issue number10
DOIs
Publication statusPublished - 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Transforming growth Factor-β-Independent role of connective tissue growth factor in the development of liver fibrosis'. Together they form a unique fingerprint.

Cite this