TGF-β/Smad and Renal Fibrosis.

Abstract

Renal fibrosis is characterized by excessive deposition of extracellular matrix (ECM) that disrupts and replaces functional parenchyma, which leads to organ failure. It is known as the major pathological mechanism of chronic kidney disease (CKD). Although CKD has an impact on no less than 10% of the world population, therapeutic options are still limited. Regardless of etiology, elevated TGF-β levels are highly correlated with the activated pro-fibrotic pathways and disease progression. TGF-β, the key driver of renal fibrosis, is involved in a dynamic pathophysiological process that leads to CKD and end-stage renal disease (ESRD). It is becoming clear that epigenetics regulates renal programming, and therefore, the development and progression of renal disease. Indeed, recent evidence shows TGF-β1/Smad signaling regulates renal fibrosis via epigenetic-correlated mechanisms. This review focuses on the function of TGF-β/Smads in renal fibrogenesis, and the role of epigenetics as a regulator of pro-fibrotic gene expression.