Tmem30a protects against podocyte injury through suppression of pyroptosis
Yanpei Hou,
Sipei Chen,
Lei Peng,
Liming Huang,
Huijian Zhang,
Ping Zhang,
Min Yu,
Lin Xiong,
Xiang Zhong,
Wenjing Liu,
Xianjun Zhu,
Li Wang,
Yi Li,
Guisen Li
Affiliations
Yanpei Hou
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Sipei Chen
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Lei Peng
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Liming Huang
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Huijian Zhang
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Ping Zhang
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Min Yu
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Lin Xiong
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Xiang Zhong
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Wenjing Liu
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
Xianjun Zhu
Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
Li Wang
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China
Yi Li
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China; Corresponding author
Guisen Li
Department of Nephrology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Sichuan Clinical Research Center for Kidney Diseases, Chengdu 610072, China; Corresponding author
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.
