CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts

✍ Scribed by Devashish Kothapalli; Gary R. Grotendorst

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 195 KB
• Volume: 182
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(200001)182:1<119::aid-jcp13>3.0.co;2-4

✦ Synopsis

Connective tissue growth factor (CTGF) is a 38-kDa cysteine-rich peptide, whose synthesis and secretion are selectively induced by transforming growth factor beta (TGF-␤) in connective tissue cells. Previous studies have demonstrated that CTGF functions as a downstream mediator of TGF-␤ mitogenic activity, where it controls cell cycle progression through late G1 and S-phase entry of NRK fibroblast suspension cultures. Here we report that CTGF induces this S-phase entry by upregulating cyclin A levels. The molecular mechanism for cyclin A induction appears to be via reduction of p27 Kip1 levels, which results in hyperphosphorylation of pRb and release of E2F, a known modulator of cyclin A gene transcription. These data indicate that CTGF acts as a mediator of TGF-␤-induced fibroblast proliferation in suspension cultures by regulating cdk activities.