Hydrogen peroxide is a novel inducer of connective tissue growth factor

Connective tissue growth factor (CTGF) has recently been described as a fib rogenic factor and is greatly induced by various extracellular stimuli, suc h as transforming growth factor-beta (TGF-beta), dexamethasone, and seroton in. CTGF induces collagen type I and fibronectin, and the deposition of suc h molecules leads to fibrotic disease in many tissues. Intracellular reacti ve oxygen species (ROS) are generated by ext acellular stress conditions an d are produced as by-products of cellular metabolism, Imbalanced cellular r edox status is a potent pathogenic factor that leads to various degenerativ e diseases, including tissue fibrosis. Since CTGF is believed to play a cru cial role in fibrotic disease formation in many tissues, we examined the ro le of ROS in CTGF gene expression in human lens epithelial cell Line B3. Th e results showed that CTGF was induced by reactive oxygen species such as h ydrogen peroxide and hydroxyl radicals. Next, we examined whether CTGF indu ction by ROS is via newly synthesized TGF-beta. The results showed that ROS directly induced CTGF mRNA not via the increased TGF-beta synthesis or act ivation. Next, we treated AG490, which is the well-known inhibitor of Janus kinase (JAK), with hydrogen peroxide. AG490 abrogated the CTGF induction b y ROS in a dose-dependent manner. The results suggest that JAK-2/-3 seems t o be involved in the enhanced CTGF mRNA expression by hydrogen peroxide. In this report, we present that hydrogen peroxide is a novel inducer of CTGF gene expression and that JAK-2/-3 activation seems to play a role in CTGF i nduction. (C) 2001 Academic Press.