title: Rescue of mesangial cells from high glucose-induced over-proliferation and extracellular matrix secretion by hydrogen sulfide.
abstract: 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.
  
  
  CONCLUSIONS
  Suppressed CSE-catalyzed endogenous H(2)S production in the kidney by hyperglycemia may play an important role in the pathogenesis of DN.
authors.affiliation: Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University Shanghai 200032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yuan
authors.forename: Hong
authors.initials: H
authors.lastname: Xue
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Linping
authors.initials: L
authors.lastname: Qu
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ni
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.forename: Tai
authors.initials: T
authors.lastname: Yao
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Limin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013549:Sweetening Agents / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D053773:Transforming Growth Factor beta1; D005947:Glucose; D006862:Hydrogen Sulfide