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FGF21 Inhibits Hypoxia/Reoxygenation-induced Renal Tubular Epithelial Cell Injury by Regulating the PPARγ/NF-κB Signaling Pathway

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Abstract

As a predominant trigger of acute kidney injury, renal ischemia-reperfusion injury can cause permanent renal impairment, and the effective therapies are lacking. Fibroblast growth factor 21 (FGF21) plays a critical regulatory role in a variety of biological activities. This study was conducted to explore the functional of FGF21 in renal ischemia-reperfusion injury and to discuss the hidden reaction mechanism. To simulate renal ischemia-reperfusion injury in vitro, HK2 cells were induced by hypoxia/reoxygenation (H/R). The effects of FGF21 on H/R-induced HK2 cell viability were evaluated utilizing cell counting kit-8 (CCK-8). The levels of lactate dehydrogenase (LDH) and inflammatory cytokines in H/R-induced HK2 cells were assessed by means of LDH assay and enzyme-linked immunosorbent assay (ELISA). The levels of oxidative stress markers were appraised with corresponding assay kits and western blot was applied to estimate the expressions of oxidative stress-related proteins. The apoptosis of H/R-induced HK2 cells was assessed by virtue of flow cytometry. The expressions of apoptosis- and PPARγ/NF-κB signaling pathway-related proteins were evaluated with western blot. To discuss the reaction mechanism of PPARγ/NF-κB pathway in H/R-induced HK2 cells, PPARγ inhibitor GW9662 was employed to treat cells and the above experiments were then conducted again. This study found that FGF21 treatment inhibited the inflammatory response, oxidative stress and apoptosis in H/R-induced HK2 cells. Moreover, FGF21 regulated PPARγ/NF-κB signaling pathway and GW9662 partially reversed the impacts of FGF21 on the inflammatory response, oxidative stress and apoptosis in H/R-exposed HK2 cells. Collectively, FGF21 protected against H/R-induced renal tubular epithelial cell injury by regulating the PPARγ/NF-κB signaling pathway.

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Data availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Author Contributions

Ruixue Li conceived and designed the study. Ruixue Li and Xi Liu performed the experiments. Ruixue Li and Xi Liu were major contributors to write the manuscript. Both authors have read and approved the final manuscript. Ruixue Li confirmed the authenticity of the raw data.

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  1. Nephrology Department, The People’s Hospital of Yubei District of Chongqing, Chongqing, 401120, PR China

    Ruixue Li & Xi Liu

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Li, R., Liu, X. FGF21 Inhibits Hypoxia/Reoxygenation-induced Renal Tubular Epithelial Cell Injury by Regulating the PPARγ/NF-κB Signaling Pathway. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01242-8

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