Journal
NEPHROLOGY DIALYSIS TRANSPLANTATION
Volume 16, Issue 6, Pages 1139-1148Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ndt/16.6.1139
Keywords
CTGF; extracellular matrix; mesangial; migration; TGF beta wound healing
Categories
Ask authors/readers for more resources
Background. Connective tissue growth factor (CTGF) is a profibrotic growth factor, which is upregulated in wound healing and renal fibrosis, including anti-Thy-1.1 nephritis. The kinetics of CTGF mRNA expression in anti-Thy-1.1 nephritis suggested that CTGF regulation might contribute to glomerular response to injury downstream of transforming growth factor-beta (TGF beta). In anti-Thy-1.1 nephritis the initial damage is followed by mesangial repair and limited sclerosis, which involves mesangial cell (MC) activation (x-smooth-muscle actin (alpha SMA) expression), proliferation, migration, and extracellular matrix production. The present in vitro study addresses the possible role of CTGF in these different aspects of mesangial response to injury, and how CTGF activity might relate to effects of TGF beta and platelet-derived growth factor-BE (PDGF-BE). Methods and Results. Immunostaining and ELISA showed that alpha SMA expression acid transformation of MC into myofibroblast-like cells was induced by TGF beta, but not affected by PDGF-BB, CTGF, or neutralizing anti-CTGF antibodies. [H-3]thymidine incorporation and Ki67 staining demonstrated that. unlike PDGF-BB, neither CTGF nor TGF beta induced the proliferation of MC. In contrast, both CTGF and TGF beta induced MC migration, as evidenced by approximation of wound edges in scrape-wounded, non-proliferating rat MC monolayers. In addition, fibronectin expression was upregulated by both CTGF and TGF beta, as measured by dot-blot analysis. Anti-CTGF completely blocked the effect of added CTGF. Moreover, anti-CTGF significantly reduced TGF beta -induced increase in fibronectin. Conclusion. It thus appears that CTGF is specifically involved in a subset of the adaptive changes of MC involved in mesangial repair and sclerosis, which makes it an interesting candidate target for future intervention strategies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available