Involvement of hydrogen sulfide and homocysteine transsulfuration pathway in the progression of kidney fibrosis after ureteral obstruction

被引：78

作者：

Jung, Kyong-Jin ^{[1
]}

Jang, Hee-Seong ^{[1
,2
]}

Kim, Jee In ^{[1
,2
]}

Han, Sang Jun ^{[1
]}

Park, Jeen-Woo ^{[3
]}

Park, Kwon Moo ^{[1
,2
]}

机构：

[1] Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700422, South Korea

[2] Kyungpook Natl Univ, Sch Med, Cardiovasc Res Inst, Taegu 700422, South Korea

[3] Kyungpook Natl Univ, Coll Nat Sci, Sch Life Sci & Biotechnol, Taegu 702701, South Korea

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2013年 / 1832卷 / 12期

基金：

新加坡国家研究基金会;

关键词：

Hydrogen sulfide; Fibrosis; Oxidative stress; NF-kappa B; TGF-beta; Cystathionine beta-synthase; MARROW-DERIVED CELLS; INJURY; PROLIFERATION; MECHANISMS; APOPTOSIS; ISCHEMIA; PROTECTS; FAILURE; DISEASE; STRESS;

D O I：

10.1016/j.bbadis.2013.06.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hydrogen sulfide (H2S) produced by cystathionine p-synthase (CBS) and cystathionine gamma-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-beta 1, activated Smad3, and activated NF-kappa B. 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. (C) 2013 Elsevier B.V. All rights reserved.

引用

页码：1989 / 1997

页数：9

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