title: Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.
abstract: Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-β-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.
authors.affiliation: 1] Institute of Neuroscience, Soochow University, Suzhou, China [2] Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Shi
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, China.
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA.
authors.forename: Hanjing
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Shen
authors.affiliation: 1] Institute of Neuroscience, Soochow University, Suzhou, China [2] Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
authors.affiliation: 1] Institute of Neuroscience, Soochow University, Suzhou, China [2] Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China [3] Department of Pharmacology, School of Pharmaceutical Science, Soochow University, Suzhou, China.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Hu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004261:DNA Replication / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D003094:Collagen; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D016207:Cytokines; D006862:Hydrogen Sulfide; D018836:Inflammation Mediators; D020928:Mitogen-Activated Protein Kinases; D013440:Sulfides; C498862:Acta2 protein, rat; C025451:sodium bisulfide