Diabetic nephropathy: A potential savior with 'rotten-egg' smell

Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease. Despite optimal management, DN is still a major contributor to morbidity and mortality of diabetic patients worldwide. The major pathological alterations in DN include excessive accumulation and deposition of extracellular matrix, leading to expansion of mesangial matrix, thickening of glomerular basement membrane and tubulointerstitial fibrosis. At the molecular level, accumulating evidence suggests that hyperglycemia or high glucose mediates renal injury in DN via multiple molecular mechanisms such as induction of oxidative stress, upregulation of renal transforming growth factor beta-1 expression, production of proinflammatory cytokines, activation of fibroblasts and renin angiotensin system, and depletion of adenosine triphosphate. Also worrying is the fact that existing therapies only retard the disease progression but do not prevent it. Therefore, there is urgent need to identify novel therapies to target additional disease mechanisms. Hydrogen sulfide (H2S), the third member of the gasotransmitter family, has recently been identified and demonstrated to possess important therapeutic characteristics that prevent the development and progression of DN in experimental animals by targeting several important molecular pathways, and therefore may represent an alternative or additional therapeutic approach for DN. This review discusses recent experimental findings on the molecular mechanisms underlying the therapeutic effects of H2S against the development and progression of DN and its clinical application in the future. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.