title: Involvement of hydrogen sulfide and homocysteine transsulfuration pathway in the progression of kidney fibrosis after ureteral obstruction.
abstract: Hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in the transsulfuration pathway of homocysteine plays a number of pathophysiological roles. Hyperhomocysteinemia is involved in kidney fibrosis. However, the role of H2S in kidney fibrosis remains to be defined. Here, we investigated the role of H2S and its acting mechanism in unilateral ureteral obstruction (UO)-induced kidney fibrosis in mice. UO decreased expressions of CBS and CSE in the kidney with decrease of H2S concentration. Treatment with sodium hydrogen sulfide (NaHS, a H2S producer) during UO reduced UO-induced oxidative stress with preservations of catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) expression, and glutathione level. In addition, NaHS mitigated decreases of CBS and CSE expressions, and H2S concentration in the kidney. NaHS treatment attenuated UO-induced increases in levels of TGF-β1, activated Smad3, and activated NF-κB. This study provided the first evidence of involvement of the transsulfuration pathway and H2S in UO-induced kidney fibrosis, suggesting that H2S and its transsulfuration pathway may be a potential target for development of therapeutics for fibrosis-related diseases.
authors.affiliation: Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Kyong-Jin
authors.initials: KJ
authors.lastname: Jung
authors.forename: Hee-Seong
authors.initials: HS
authors.lastname: Jang
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kim
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Han
authors.forename: Jeen-Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D018450:Disease Progression; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D013440:Sulfides / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D000099156:Superoxide Dismutase 2
chemical_list: D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D006710:Homocysteine; D006861:Hydrogen Peroxide; D006862:Hydrogen Sulfide; D016328:NF-kappa B; D013440:Sulfides; D013482:Superoxide Dismutase; D013481:Superoxides; D053773:Transforming Growth Factor beta1; D000099156:Superoxide Dismutase 2
keywords: 3-mercaptopyruvate sulphurtransferase; 4% paraformaldehyde, 75mMl-lysine, 10mM sodium periodate; 4-HNE; 4-hydroxynonenal; 5,5-dithiobis (2-nitrobenzoic acid); 5-thio-2-nitrobenzoic acid; CBS; CSE; Cystathionine β-synthase; DHE; DL-propargylglycine; DTNB; ESRD; Fibrosis; GFR; GSSG; HA; Hydrogen sulfide; MDA; MPS; NF-κB; Oxidative stress; PAG; PCr; PLP; TBA; TBARS; TGF-β; UO; alpha-smooth muscle actin; cystathionine β-synthase; cystathionine γ-lyase; dihydroethidium; end-stage renal disease; glomerular filtration rate; hydroxylamine; malondialdehyde; oxidized glutathione; plasma creatinine; thiobarbituric acid-reactive substances; ureteral obstruction; α-SMA