Tmem30a protects against podocyte injury through suppression of pyroptosis

Podocytopathies, such as focal segmental glomerulosclerosis (FSGS), are characterized by podocyte injury and can easily progress to end-stage kidney disease. However, the mechanisms underlying podocyte injury remain unclear. We observed podocyte injury along with pyroptosis in patients with FSGS. Bi...

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Published iniScience Vol. 27; no. 6; p. 109976
Main Authors Hou, Yanpei, Chen, Sipei, Peng, Lei, Huang, Liming, Zhang, Huijian, Zhang, Ping, Yu, Min, Xiong, Lin, Zhong, Xiang, Liu, Wenjing, Zhu, Xianjun, Wang, Li, Li, Yi, Li, Guisen
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 21.06.2024
Elsevier
Subjects
biological sciences
cell biology
molecular biology
nephrology
nephrology
molecular biology
cell biology
biological sciences
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Summary:Podocytopathies, such as focal segmental glomerulosclerosis (FSGS), are characterized by podocyte injury and can easily progress to end-stage kidney disease. However, the mechanisms underlying podocyte injury remain unclear. We observed podocyte injury along with pyroptosis in patients with FSGS. Bioinformatic analysis of public datasets revealed that transmembrane protein 30a (Tmem30a) might be associated with FSGS. The expression of Temem30a and the podocyte-related protein, nephrin, were significantly downregulated in patients with FSGS, adriamycin (ADR)-induced mice, and podocyte-specific Tmem30aloxP/loxP; NPHS2-Cre mice, whereas the expression of NLR family pyrin domain containing 3 (NLRP3) and ASC, two pyroptosis-related proteins, were significantly upregulated. Meanwhile, the pyroptosis inhibitor MCC950 and disulfiram (DSF) increased Tmem30a and podocyte-related proteins expression, and inhibited pyroptosis-related proteins expression in ADR-induced mouse podocytes and Tmem30a knockdown (KD) mouse podocytes. Therefore, Tmem30a might protect against podocyte injury by inhibiting pyroptosis, suggesting a potential therapeutic target for podocytopathies. [Display omitted] •Tmem30a was downregulated in FSGS patients and ADR-induced podocyte injury models•Loss of Tmem30a expression induces podocyte injury by activating pyroptosis•MCC950 and DSF alleviates podocyte injury by inhibiting pyroptosis Nephrology; Biological sciences; Molecular biology; Cell biology
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109976