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- Title
Tetrandrine alleviates podocyte injury via calcium-dependent calpain-1 signaling blockade.
- Authors
Ding, Yin; Tang, Xuanli; Wang, Yuhui; Yu, Dongrong; Zhu, Caifeng; Yu, Jin
- 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.
- Subjects
IN vitro studies; STATISTICS; IN vivo studies; CALCIUM antagonists; ANIMAL experimentation; DOXORUBICIN; WESTERN immunoblotting; ISOQUINOLINE; PROTEOLYTIC enzymes; RATS; T-test (Statistics); CELL survival; TREATMENT effectiveness; PROTEINURIA; MESSENGER RNA; DESCRIPTIVE statistics; RESEARCH funding; EPITHELIAL cells; DATA analysis software; DATA analysis; MICE; DIABETIC nephropathies; PHARMACODYNAMICS
- Publication
BMC Complementary Medicine & Therapies, 2021, Vol 21, Issue 1, p1
- ISSN
2662-7671
- Publication type
Article
- DOI
10.1186/s12906-021-03469-x