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ORIGINAL RESEARCH article

Front. Med.
Sec. Nephrology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1381479

Adriamycin-induced podocyte injury via the Sema3A/TRPC5/RAC1 pathway

Provisionally accepted
Yan Liu Yan Liu 1Ri L. Ge Ri L. Ge 1*Zhen Z. Shan Zhen Z. Shan 1*Yan J. Wang Yan J. Wang 2Yan Y. Yang Yan Y. Yang 2*Xue Sun Xue Sun 1Peng L. Luo Peng L. Luo 1*
  • 1 Qinghai University, Xining, Qinghai Province, China
  • 2 Affiliated Hospital of Qinghai University, Xining, Qinghai Province, China

The final, formatted version of the article will be published soon.

    Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A(Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycininduced foot process fusion and urine protein. These results contribute to a deeper

    Keywords: Podocytopathy, SEMA3A, podocyte, TRPC5, Foot process effacement

    Received: 18 Feb 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Liu, Ge, Shan, Wang, Yang, Sun and Luo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ri L. Ge, Qinghai University, Xining, 810016, Qinghai Province, China
    Zhen Z. Shan, Qinghai University, Xining, 810016, Qinghai Province, China
    Yan Y. Yang, Affiliated Hospital of Qinghai University, Xining, Qinghai Province, China
    Peng L. Luo, Qinghai University, Xining, 810016, Qinghai Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.