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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- 1 Qinghai University, Xining, Qinghai Province, China
- 2 Affiliated Hospital of Qinghai University, Xining, Qinghai Province, China
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
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