Sirtuin1通过PGC-1α介导的转录共激活抑制肾近端小管细胞铁凋亡,从而抑制钙草酸盐肾病的发生

IF 14.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Chen Duan, Bo Li, Haoran Liu, Yangjun Zhang, Xiangyang Yao, Kai Liu, Xiaoliang Wu, Xiongmin Mao, Huahui Wu, Zhenzhen Xu, Yahua Zhong, Zhiquan Hu, Yan Gong, Hua Xu
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引用次数: 0

摘要

草酸钙(CaOx)结晶会导致肾小管上皮细胞损伤,进而引发肾病。然而,其潜在机制仍不清楚。本研究对草酸钙肾炎小鼠的肾脏样本进行了单细胞转录组测序。结果发现,肾近曲小管细胞是受损最严重的细胞群,并伴有高铁蛋白血症。进一步的研究表明,sirtuin1(Sirt1)能以谷胱甘肽过氧化物酶 4(GPX4)依赖的方式有效减少铁蛋白沉积和钙氧化物晶体诱发的肾损伤。从机理上讲,Sirt1依赖于过氧化物酶体增殖激活受体γ辅助激活剂1α(PGC-1α)来促进肾小管上皮细胞抵抗铁蛋白沉积,而PGC-1α可以招募核因子红细胞2相关因子2(NRF2)到GPX4的启动子区域,共同激活GPX4的转录。这项研究为了解钙氧化物晶体诱导肾损伤的机制提供了新的视角,并确定了 Sirt1 和 PGC-1α 作为晶体性肾病的潜在预防和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sirtuin1 Suppresses Calcium Oxalate Nephropathy via Inhibition of Renal Proximal Tubular Cell Ferroptosis Through PGC-1α-mediated Transcriptional Coactivation

Sirtuin1 Suppresses Calcium Oxalate Nephropathy via Inhibition of Renal Proximal Tubular Cell Ferroptosis Through PGC-1α-mediated Transcriptional Coactivation

Sirtuin1 Suppresses Calcium Oxalate Nephropathy via Inhibition of Renal Proximal Tubular Cell Ferroptosis Through PGC-1α-mediated Transcriptional Coactivation

Calcium oxalate (CaOx) crystals induce renal tubular epithelial cell injury and subsequent nephropathy. However, the underlying mechanisms remain unclear. In the present study, single-cell transcriptome sequencing is performed on kidney samples from mice with CaOx nephrocalcinosis. Renal proximal tubular cells are identified as the most severely damaged cell population and are accompanied by elevated ferroptosis. Further studies demonstrated that sirtuin1 (Sirt1) effectively reduced ferroptosis and CaOx crystal-induced kidney injury in a glutathione peroxidase 4 (GPX4)-dependent manner. Mechanistically, Sirt1 relies on peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) to promote resistance to ferroptosis in the tubular epithelium, and PGC-1α can recruit nuclear factor erythroid 2-related factor 2 (NRF2) to the promoter region of GPX4 and co-activate GPX4 transcription. This work provides new insight into the mechanism of CaOx crystal-induced kidney injury and identifies Sirt1 and PGC-1α as potential preventative and therapeutic targets for crystal nephropathies.

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来源期刊
Advanced Science
Advanced Science CHEMISTRY, MULTIDISCIPLINARYNANOSCIENCE &-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
18.90
自引率
2.60%
发文量
1602
审稿时长
1.9 months
期刊介绍: Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.
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