Rescue of mesangial cells from high glucose induced over proliferation and extracellular matrix secretion by H_2S

【摘要】：正Hydrogen sulfide(H_2S) is considered the third gasotransmitter after nitric oxide and carbon monoxide. This gas molecule has been reported to participate in renal function regulation.Diabetic nephropathy is one of the major chronic complications of diabetes.The present study aimed to explore the changes in H_2S metabolism in the early stage of diabetic nephropathy and the effects of H_2S on cultured rat renal glomerular mesangial cells(MCs). Cultured rat MCs and streptozotocin(STZ) injection-induced diabetic rats were used in the experiment.Expression levels of cystathionineγ-lyase(CSE),transforming growth factor-β1(TGF-β1) and collagen IV in rat renal cortex and cultured MCs were measured by quantitative real time PCR(qRT-PCR) and Western blot.Reactive oxygen species(ROS) released from rat MCs was assessed by fluorescent probe assays.MCs proliferation was analyzed by 5'-bromo-2'-deoxyuridine incorporation assay.H_2S levels in plasma and renal cortex and the levels of CSE mRNA and protein renal cortex were significantly reduced,while the levels of TGF-β1 and collagen IV increased, 3 weeks after STZ injection.Administration of NaHS,a H_2S donor,reversed the increase in TGF-β1 and collagen IV levels in diabetic rats.In cultured MCs,high glucose media promoted ROS generation and cell proliferation, upregulated TGF-β1 and collagen IV expression,but decreased CSE expression significantly.Treatment of the cultured cells with NaHS reversed the effect of high glucose.Reduction of endogenous H_2S generation by DL-propargylglycine, a CSE inhibitor,evoked similar cellular effects of high glucose,including promoted cell proliferation, increased TGF-β1 and collagen IV expressions,and ROS generation.Suppressed CSE-catalyzed endogenous H_2S production in the kidney by hyperglycemia may play an important role in the pathogenesis of diabetic nephropathy.