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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Research

Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade

Authors: Yin Ding, Xuanli Tang, Yuhui Wang, Dongrong Yu, Caifeng Zhu, Jin Yu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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Abstract

Background

Podocytes have become a crucial target for interventions in proteinuric kidney diseases. Many studies have reported that overexpression of transient receptor potential cation channel protein 6 (TRPC6) in podocyte injury upregulates intracellular Ca2+ influx and stimulates Ca2+-dependent protease calpain-1 signaling. The traditional Chinese drug, tetrandrine, a nonselective Ca2+ channel blocker, has long been used to treat chronic kidney disease. This research aimed to explore the possible mechanisms underlying the anti-proteinuric properties of tetrandrine.

Methods

We investigated the involvement of tetrandrine in Ca2+ dependent calpain-1 signaling in mouse podocytes and adriamycin-induced nephropathy rats. Cyclosporine A (CsA) and U73122 were used as positive controls. Cell viability, cytotoxicity, Ca2+ concentration, calpain activity, and mRNA and protein expression levels of calpain-1 signaling pathways were examined. The clinical and pathological changes were measured.

Results

Tetrandrine decreased intracellular Ca2+ influx in cultured TRPC6-overexpressing podocytes. In both in vitro and in vivo studies, the administration of tetrandrine downregulated calpain activity and the expression of calpain-1 and restored the expression of downstream Talin-1 and nephrin. Compared to CsA, tetrandrine treatment exhibited superior inhibitory effects on calpain activity and calpain-1 expression.

Conclusions

Tetrandrine has therapeutic potential in podocyte damage by blocking Ca2+-dependent activation of the calpain-1 signaling pathway. Tetrandrine reduced proteinuria, improved renal function, and alleviate renal pathological damage.
Appendix
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Metadata
Title
Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade
Authors
Yin Ding
Xuanli Tang
Yuhui Wang
Dongrong Yu
Caifeng Zhu
Jin Yu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-021-03469-x

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