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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1523855

CAV1 promotes epithelial-to-mesenchymal transition (EMT) and chronic renal allograft interstitial fibrosis by activating the ferroptosis pathway

Provisionally accepted
Qianguang Han Qianguang Han 1Bin Ni Bin Ni 2Wei Bao Wei Bao 2Junqi Zhang Junqi Zhang 2Ming Zheng Ming Zheng 2Jinxu Miu Jinxu Miu 2Zijie Wang Zijie Wang 1Jingwen Yuan Jingwen Yuan 1Jun Tao Jun Tao 1Zhi Jian Han Zhi Jian Han 1Min Gu Min Gu 2Xiaobing Ju Xiaobing Ju 1Ruoyun Tan Ruoyun Tan 1*
  • 1 Department of Urology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China
  • 2 Department of Urology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Liaoning Province, China

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

    Background: Chronic allograft dysfunction (CAD) stands as a critical factor that limits the longterm viability of transplanted kidneys. Ferroptosis is an iron-dependent form of programmed cell death increasingly linked to chronic fibrosis. However, the mechanism by which ferroptosis contributes to the onset and progression of CAD remains unclear.Methods: This study analyzed transcriptome data from renal transplant biopsy samples in the Gene Expression Omnibus (GEO), through clinical samples, animal models, and cell experiments, this study investigated the mechanism by which Caveolin-1 (CAV1) promotes CAD through the regulation of the ferroptosis pathway.The elevated levels of CAV1 were found to positively correlate with CAD incidence. Clinical and animal model validation confirmed heightened CAV1 expression in CAD. In vitro experiments demonstrated that CAV1 can directly promote chronic renal allograft interstitial fibrosis by regulating ferroptosis in renal tubular epithelial cells; additionally, it can promote epithelial-tomesenchymal transition (EMT) by secreting Interleukin-6 (IL-6), thereby further contributing to CAD. Conclusion: CAV1 plays a critical role in the development of CAD by promoting EMT and chronic renal allograft interstitial fibrosis through the ferroptosis pathway. Adjusting ferroptosis by altering the expression abundance of CAV1 may become an important method for the prevention and treatment of CAD in the future.

    Keywords: Chronic renal graft dysfunction (CAD), Epithelial-mesenchymal transition (EMT), ferroptosis, Caveolin-1(CAV1), Interleukin-6 (IL-6)

    Received: 06 Nov 2024; Accepted: 21 Jan 2025.

    Copyright: © 2025 Han, Ni, Bao, Zhang, Zheng, Miu, Wang, Yuan, Tao, Han, Gu, Ju and Tan. 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: Ruoyun Tan, Department of Urology, First Affiliated Hospital, Nanjing Medical University, Nanjing, 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.