机构：[1]Institute of Neuroscience, Soochow University, Suzhou, China[2]Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China[3]Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia, USA[4]Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou, China[5]Department of Pharmacology, School of Pharmaceutical Science, Soochow University, Suzhou, China
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-beta-synthase, a hydrogen sulfide producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-gamma-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 a-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1 beta, tumor necrosis factor-alpha, 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-beta 1-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.
基金：
This work was supported by the
research grants from the National Natural Science Foundation of
China (81200495/2012 to KS and 81171212 to LF-H) and the start-up
funding for imported overseas talents of Soochow University
(Q421500210), and was also funded by a project funded by the
Priority Academic Program Development of Jiangsu Higher Education
Institutions (PAPD). HP was supported by the Center for Diagnostics
and Therapeutics (CDT) program and Georgia State University
Fellowship through the CDT.
第一作者机构：[1]Institute of Neuroscience, Soochow University, Suzhou, China[2]Department of Nephrology, Second Affiliated Hospital of Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Neurology, Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, China.[*2]Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Kai Song,Fen Wang,Qian Li,et al.Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy[J].KIDNEY INTERNATIONAL.2014,85(6):1318-29.doi:10.1038/ki.2013.449.
APA：
Kai Song,Fen Wang,Qian Li,Yong-Bing Shi,Hui-Fen Zheng...&Li-Fang Hu.(2014).Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy.KIDNEY INTERNATIONAL,85,(6)
MLA：
Kai Song,et al."Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy".KIDNEY INTERNATIONAL 85..6(2014):1318-29
医学