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

iScience (Jun 2024)

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

Journal volume & issue: Vol. 27, no. 6
p. 109976

Abstract

Read online

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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords