ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1577625
This article is part of the Research TopicCancer, Metabolism and Kidney Injury: From Molecular Mechanisms to TherapyView all 3 articles
Overexpression of GDF15 Protects Kidneys from Ischemia Reperfusion Injury and affects circular RNA expression
Provisionally accepted
Cuilin Zhu1,2*
Qing Liu3Yale Su1,2Yixin Zhang1,2
Aanal Patel2Adam Greasley2Jifu Jiang2Douglas Quan2
Weiping Min2
Kexiang Liu1
Xiufen Zheng2- 1Second Affiliated Hospital of Jilin University, Changchun, China
- 2Western University, London, Ontario, Canada
- 3Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Beijing, China
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Background: Renal failure and dysfunction remain one of the most significant morbidities impacting patient's life. Effective treatments still lack in the context of an increasing number of patients with renal failure. This study aims to investigate the impact of growth differentiation factor 15 (GDF15) in treating renal dysfunction and to explore its therapeutic potential.Methods: Renal injury was induced with a murine ischemia reperfusion injury (IRI) model. Mice overexpressing GDF15 (GDF15 transgenic (GDF15TG) mice, GDF15 knock out (GDF15 KO) mice and wild type (WT) mice all underwent IRI to test the effects of GDF15 on renal injury. Renal function and histopathological changes were measured 24h after reperfusion. Cell apoptosis was detected by TUNEL and tissue inflammation was detected by myeloperoxidase (MPO) activity. qRT-PCR was conducted to determine the expression of genes and circular RNAs.deficiency increased the mortality. GDF15TG mice had better renal function with the lower levels of blood creatinine and blood urea nitrogen (BUN). Over-expression of GDF15 reduces kidney pathological changes, cell apoptosis, neutrophil infiltration and mortality. Over-expression of GDF15 also decreased the expression of apoptotic genes (high mobility group 1, HMGA1 and Bax), inflammatory genes IL-1β, IL-6, tumor necrosis factor (TNF-α), chemokine 1 (CK1), and senescent gene p21 whereas increases Bcl-XL, Importin 11 and Crim1. IRI upregulated circular RNA Smad3 and reduced circular RNA Hipk3 and circular RNA Crim1, which was offset by GDF15.Over-expression of GDF15 protects renal function and prevents renal failure, highlighting its potential in treating renal failure.
Keywords: GDF15, ischemia reperfusion injury, Kidney, Apoptosis, Inflammation, circular RNA
Received: 17 Feb 2025; Accepted: 30 May 2025.
Copyright: © 2025 Zhu, Liu, Su, Zhang, Patel, Greasley, Jiang, Quan, Min, Liu and Zheng. 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: Cuilin Zhu, Second Affiliated Hospital of Jilin University, Changchun, China
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