title: Hydrogen sulfide accelerates the recovery of kidney tubules after renal ischemia/reperfusion injury.
abstract: BACKGROUND
  Progression of acute kidney injury to chronic kidney disease (CKD) is associated with inadequate recovery of damaged kidney. Hydrogen sulfide (H2S) regulates a variety of cellular signals involved in cell death, differentiation and proliferation. This study aimed to identify the role of H2S and its producing enzymes in the recovery of kidney following ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  Mice were subjected to 30 min of bilateral renal ischemia. Some mice were administered daily NaHS, an H2S donor, and propargylglycine (PAG), an inhibitor of the H2S-producing enzyme cystathionine gamma-lyase (CSE), during the recovery phase. Cell proliferation was assessed via 5'-bromo-2'-deoxyuridine (BrdU) incorporation assay.
  
  
  RESULTS
  Ischemia resulted in decreases in CSE and cystathionine beta-synthase (CBS) expression and activity, and H2S level in the kidney. These decreases did not return to sham level until 8 days after ischemia when kidney had fibrotic lesions. NaHS administration to I/R-injured mice accelerated the recovery of renal function and tubule morphology, whereas PAG delayed that. Furthermore, PAG increased mortality after ischemia. NaHS administration to I/R-injured mice accelerated tubular cell proliferation, whereas it inhibited interstitial cell proliferation. In addition, NaHS treatment reduced post-I/R superoxide formation, lipid peroxidation, level of GSSG/GSH and Nox4 expression, whereas it increased catalase and MnSOD expression.
  
  
  CONCLUSIONS
  Our findings demonstrate that H2S accelerates the recovery of I/R-induced kidney damage, suggesting that the H2S-producing transsulfuration pathway plays an important role in kidney repair after acute injury.
authors.affiliation: Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Molecular Medicine and MRC, College of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kim
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Republic of Korea.
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Anatomy, Cardiovascular Research Institute and BK21 Plus, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D000480:Alkynes; D013440:Sulfides; D013481:Superoxides; C009055:propargylglycine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine
keywords: CBS; CSE; hydrogen sulfide; ischemia; reactive oxygen species; regeneration