Renalase alleviates salt-induced kidney necroptosis and inflammation.

Autor: Wang Y; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Jia H; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Gao K; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Du MF; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Chu C; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Wang D; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Ma Q; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Hu GL; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Zhang X; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Sun Y; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China., Man ZY; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., Mu JJ; Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. mujjun@163.com.; Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, China. mujjun@163.com.
Jazyk: angličtina
Zdroj: Hypertension research : official journal of the Japanese Society of Hypertension [Hypertens Res] 2024 Oct; Vol. 47 (10), pp. 2811-2825. Date of Electronic Publication: 2024 Aug 08.
DOI: 10.1038/s41440-024-01814-4
Abstrakt: Recent evidence suggests that necroptosis may contribute to the development of kidney injury. Renalase is a novel secretory protein that exerts potent prosurvival and anti-inflammatory effects. We hypothesized that renalase could protect the kidney from salt-induced injury by modulating necroptosis. High salt and renalase treatments were administered to Dahl salt-sensitive (SS) rats, renalase knockout (KO) mice, and HK-2 cells. Furthermore, a cohort of 514 eligible participants was utilized to investigate the association between single nucleotide polymorphisms (SNPs) in the genes RIPK1, RIPK3, and MLKL, and the risk of subclinical renal damage (SRD) over 14 years. A high-salt diet significantly increased the expression of key components of necroptosis, namely RIPK1, RIPK3, and MLKL, as well as the release of inflammatory factors in SS rats. Treatment with recombinant renalase reduced both necroptosis and inflammation. In renalase KO mice, salt-induced kidney injury was more severe than in wild-type mice, but supplementation with renalase attenuated the kidney injury. In vitro experiments with HK-2 cells revealed high salt increased necroptosis and inflammation. Renalase exhibited a dose-dependent decrease in salt-induced necroptosis, and this cytoprotective effect was negated by the knockdown of PMCA4b, which is the receptor of renalase. Furthermore, the cohort study showed that SNP rs3736724 in RIPK1 and rs11640974 in MLKL were significantly associated with the risk of SRD over 14 years. Our analysis shows that necroptosis plays a significant role in the development of salt-induced kidney injury and that renalase confers its cytoprotective effects by inhibiting necroptosis and inflammation.
(© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)
Databáze: MEDLINE
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