NADPH oxidase-dependent redox signaling in TGF-beta-mediated fibrotic responses

Uncontrolled fibrosis in organs like heart, kidney, liver and lung is detrimental and may lead to end-stage organ failure. Currently there is no effective treatment for fibrotic disorders. Transforming growth factor (TGF)-beta has a fundamental role in orchestrating the process of fibrogenesis; however, interventions directly targeting TGF-beta would have undesired systemic side effects due to the multiple physiological functions of TGF-beta. Further characterization of the downstream signaling pathway(s) involved in TGF-beta-mediated fibrosis may lead to discovery of novel treatment strategies for fibrotic disorders. Accumulating evidence suggests that Nox4 NADPH oxidase may be an important downstream effector in mediating TGF-beta-induced fibrosis, while NADPH oxidase-dependent redox signaling may in turn regulate TGF-beta/Smad signaling in a feed-forward manner. It is proposed that pharmacological inhibition of the Nox4 function may represent a novel approach in treatment of fibrotic disorders. (C) 2014 The Authors. Published by Elsevier B.V. All rights reserved.