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Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis

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Author(s)
Sang Jun HanMi Ra NohJung-Min JungIsao IshiiJeongsoo YooJee In KimKwon Moo Park
Keimyung Author(s)
Kim, Jee In
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Free Radical Biology & Medicine
Issued Date
2017
Volume
112
Keyword
Chronic kidney diseaseCystathionine γ-lyaseHydrogen sulfideKidney fibrosisReactive oxygen species
Abstract
Cystathionine γ-lyase (CSE), the last key enzyme of the transsulfuration pathway, is involved in the production of hydrogen sulfide (H2S) and glutathione (GSH), which regulate redox balance and act as important antioxidant molecules. Impairment of the H2S- and GSH-mediated antioxidant system is associated with the progression of chronic kidney disease (CKD), characterized by kidney fibrosis and dysfunction. Here, we evaluated the role of CSE in the progression of kidney fibrosis after unilateral ureteral obstruction (UUO) using mice deficient in the Cse gene. UUO of wild-type mice reduced the expression of H2S-producing enzymes, CSE, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase in the obstructed kidneys, resulting in decreased H2S and GSH levels. Cse gene deletion lowered H2S and GSH levels in the kidneys. Deleting the Cse gene exacerbated the decrease in H2S and GSH levels and increase in superoxide formation and oxidative damage to proteins, lipids, and DNA in the kidneys after UUO, which were accompanied by greater kidney fibrosis, deposition of extracellular matrixes, expression of α-smooth muscle actin, tubular damage, and infiltration of inflammatory cells. Furthermore, Cse gene deletion exacerbated mitochondrial fragmentation and apoptosis of renal tubule cells after UUO. The data provided herein constitute in vivo evidence that Cse deficiency impairs renal the H2S- and GSH-producing activity and exacerbates UUO-induced kidney fibrosis. These data propose a novel therapeutic approach against CKD by regulating CSE and the transsulfuration pathway.
Keimyung Author(s)(Kor)
김지인
Publisher
School of Medicine (의과대학)
Citation
Sang Jun Han et al. (2017). Hydrogen sulfide-producing cystathionine γ-lyase is critical in the progression of kidney fibrosis. Free Radical Biology & Medicine, 112, 423–432. doi: 10.1016/j.freeradbiomed.2017.08.017
Type
Article
ISSN
0891-5849
Source
https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(17)30733-5
DOI
10.1016/j.freeradbiomed.2017.08.017
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41281
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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