巨噬细胞极化
细胞生物学
炎症
肾
Notch信号通路
锡尔图因
西妥因1
细胞凋亡
巨噬细胞
信号转导
草酸钙
癌症研究
生物
化学
免疫学
内科学
钙
下调和上调
内分泌学
医学
生物化学
NAD+激酶
体外
酶
基因
作者
Baofeng Song,Bojun Li,Jinying Ning,Yuqi Xia,Zehua Ye,Tian-hui Yuan,Xin-zhou Yan,Lei Li,Xiangjun Zhou,Ting Rao,Wei Li,Fan Cheng
标识
DOI:10.1016/j.intimp.2023.110398
摘要
Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.
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