睾丸特异性蛋白Y编码样蛋白2在肾损伤中的作用。
The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.
作者信息
Sui Mingxing, Yan Sijia, Zhang Pei, Li Yuhong, Chen Kewen, Li Yanhua, Lu Hanlan, Li Yanfeng, Zhao Wenyu, Zeng Li
机构信息
Department of Organ Transplantation, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Pathology, College of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
iScience. 2024 Mar 27;27(5):109594. doi: 10.1016/j.isci.2024.109594. eCollection 2024 May 17.
Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress and . Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.
肾缺血再灌注损伤（IRI）是急性肾损伤（AKI）的主要原因。最近的研究结果表明，睾丸特异性蛋白Y编码样2（TSPYL2）在糖尿病相关肾损伤中发挥促纤维化作用。然而，TSPYL2在IRI诱导的肾损伤中的作用尚不完全清楚。在本研究中，我们发现TSPYL2在AKI小鼠模型和缺氧/复氧（H/R）细胞模型中的表达上调。敲低TSPYL2可减轻IRI后的肾损伤。更具体地说，敲低TSPYL2或氨基羧基粘康酸半醛脱羧酶（ACMSD）可减轻肾IRI诱导的线粒体功能障碍和氧化应激。进一步研究表明，TSPYL2通过抑制SIRT1并促进p300活性来调节SREBP-2乙酰化，从而促进ACMSD的转录活性。总之，TSPYL2被确定为通过激活ACMSD来调节IRI诱导的肾损伤的关键调节因子，这可能导致肾脏中NAD+含量及损伤反应。
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