Sirtuin 3 suppresses the formation of renal calcium oxalate crystals through promoting M2 polarization of macrophages. Issue 7 (26th December 2018)

• Record Type: Journal Article
• Authors: Xi, Junhua; Chen, Yang; Jing, Junfeng; Zhang, Yanbin; Liang, Chaozhao; Hao, Zongyao; Zhang, Li
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 7(2019:Jul.)
• Page Start: 11463
• Page End: 11473
• Publication Date: 2018-12-26
• Subjects: calcium oxalate (CaOx) -- forkhead box O1 (FOXO1) -- kidney stone (KS) -- macrophage (Mϕs) polarization -- sirtuin 3 (SIRT3); Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27803
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: This study aims to verify whether the inhibitory effect of Sirtuin 3 (SIRT3) on the formation of renal calcium oxalate crystals was mediated through promoting macrophages (Mϕs) polarization. Identification and quantification of M1 and M2 monocytes were performed using fluorescence‐activated cell sorting analysis. SIRT3 protein level and forkhead box O1 (FOXO1) acetylation level were measured using western blot analysis. Cell apoptosis of HK‐2 was detected by flow cytometry. Mouse kidney tissues were subjected to Von Kossa staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical staining for detection of kidney crystals deposition, apoptosis, and expression of crystal‐related molecules, respectively. The results showed that human peripheral blood monocytes from patients with kidney stone (KS) exhibited decreased M2 monocytes percentage and SIRT3 expression, whereas increased FOXO1 acetylation compared with the normal controls. In vitro assay revealed that SIRT3 overexpression in bone marrow‐derived M0/M1/M2 Mϕs induced M2 polarization and decreased FOXO1 acetylation. Furthermore, FOXO1 knockdown reversed SIRT3‐mediated induction of M2 polarization and inhibition of HK‐2 (human proximal tubular cell line) apoptosis. Further in vivo experiments demonstrated that SIRT3‐overexpressing Mϕs transfusion not only induced M2 polarization, but also alleviated inflammation, apoptosis, and crystals deposition in glyoxylate‐induced KS mice. In conclusion, SIRT3 suppresses formation of renal calcium oxalate crystals through promoting M2 polarization via deacetylating FOXO1. Abstract : Our findings support the notion that Sirtuin 3 (SIRT3) suppresses renal inflammation, renal apoptosis, and formation of renal calcium oxalate crystals. The protective role of SIRT3 in kidney stone (KS) disease was mediated, at least in part, through promoting the polarization of macrophages (Mϕs) toward the M2 phenotype via deacetylating forkhead box O1 (FOXO1). This study supports the therapeutic possibility of targeted Mϕs‐phenotype shifting from M1 to M2 in KS disease.