TGF‐beta as a master regulator of diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end‐stage renal disease. TGF‐β is a pleiotropic cytokine and has been rec-ognized as a key mediator of DN. However, anti‐TGF‐β treatment for DN remains controversial due to the diverse role of TGF‐β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF‐β in the pathogenesis of DN is the initial step towards the development of anti‐TGF‐β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF‐β in DN by focusing on the latent versus active TGF‐β1, the TGF‐β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF‐β/Smad signaling in the development of DN by emphasizing Smad-dependent non‐coding RNAs including microRNAs and long‐non‐coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF‐β signaling with various therapeutic approaches are discussed.