JOURNAL ARTICLE

Rescue of mesangial cells from high glucose-induced over-proliferation and extracellular matrix secretion by hydrogen sulfide

Ping Yuan, Hong Xue, Li Zhou, Linping Qu, Cheng Li, Zhen Wang, Jun Ni, Chen Yu, Tai Yao, Yu Huang, Rui Wang, Limin Lu
Nephrology, Dialysis, Transplantation 2011, 26 (7): 2119-26
21208996

BACKGROUND: Hydrogen sulfide (H(2)S) is considered as the third gasotransmitter after nitric oxide and carbon monoxide. This gas molecule participates in the regulation of renal function. Diabetic nephropathy (DN) is one of the major chronic complications of diabetes. The present study aimed to explore the changes in H(2)S metabolism in the early stage of DN and the effects of H(2)S on cultured rat renal glomerular mesangial cells (MCs).

METHODS: Cultured rat MCs and streptozotocin (STZ)-induced diabetic rats were used in this study. Expression levels of cystathionine γ-lyase (CSE), transforming growth factor-β1 (TGF-β1) and collagen IV in rat renal cortex and in cultured MCs were determined by quantitative real-time 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.

RESULTS: H(2)S levels in the plasma and renal cortex and the levels of CSE messenger RNA (mRNA) and protein in 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(2)S donor, reversed the increases in TGF-β1 and collagen IV in diabetic rats. By contrast, NaHS did not alter the TGF-β1 and collagen IV levels in non-diabetic rats. But NaHS lowered the CSE mRNA level in renal cortex. Exposure to high glucose promoted ROS generation and cell proliferation, up-regulated the expression of TGF-β1 and collagen IV but decreased the CSE expression in cultured MCs. Treatment of cultured MCs with NaHS reversed the effect of high glucose. NaHS did not change ROS generation, cell proliferation, TGF-β1 and collagen IV expression in the cells cultured with normal glucose. Reduction of endogenous H(2)S generation by DL-propargylglycine, a CSE inhibitor, produced similar cellular effects as high glucose, including increases in cell proliferation, TGF-β1 and collagen IV expressions and ROS generation.

CONCLUSION: Suppressed CSE-catalyzed endogenous H(2)S production in the kidney by hyperglycemia may play an important role in the pathogenesis of DN.

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