Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Kai Song, Fen Wang, Qian Li, Yong Bing Shi, Hui Fen Zheng, Hanjing Peng, Hua Ying Shen, Chun Feng Liu, Li Fang Hu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1318-1329
Number of pages12
JournalKidney international
Volume85
Issue number6
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • cell signaling
  • chronic inflammation
  • chronic renal disease

ASJC Scopus subject areas

  • Nephrology

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