Tetrandrine Attenuates Podocyte Injury by Inhibiting TRPC6-Mediated RhoA/ROCK1 Pathway

Anal Cell Pathol (Amst). 2022 Sep 30:2022:7534181. doi: 10.1155/2022/7534181. eCollection 2022.

Abstract

Tetrandrine (Tet), a compound found in a traditional Chinese medicine, presents the protective effect for kidney function. Our study is aimed at clarifying the efficacy and underlying mechanism of Tet on podocyte injury. In this study, podocyte injury was induced in rats with adriamycin (ADR), and MPC5 podocytes were constructed with TRPC6 overexpression. We found that Tet treatment reduced the levels of proteinuria, serum creatinine, and blood urea nitrogen and increased plasma albumin levels in ADR-induced rats. Tet reduced intracellular Ca2+ influx and apoptosis in MPC5 podocytes overexpressing TRPC6. Tet downregulated the expression of renal TRPC6, RhoA, and ROCK1 and upregulated the expression of synaptopodin; meanwhile, it reduced calcineurin activity in vivo and in vitro. In conclusion, Tet protects against podocyte by affecting TRPC6 and its downstream RhoA/ROCK1 signaling pathway.

MeSH terms

  • Animals
  • Benzylisoquinolines
  • Calcineurin / metabolism
  • Calcineurin / pharmacology
  • Creatinine
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Podocytes* / metabolism
  • Rats
  • Serum Albumin / metabolism
  • Serum Albumin / pharmacology
  • TRPC Cation Channels / metabolism
  • TRPC Cation Channels / pharmacology
  • TRPC6 Cation Channel / metabolism
  • rho-Associated Kinases / metabolism
  • rho-Associated Kinases / pharmacology
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Benzylisoquinolines
  • Serum Albumin
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • Trpc6 protein, rat
  • tetrandrine
  • Doxorubicin
  • Creatinine
  • ROCK1 protein, rat
  • rho-Associated Kinases
  • Calcineurin
  • rhoA GTP-Binding Protein