KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS‑induced ATDC5 cells via SIRT1/NF‑κB/p53 signaling

Chen,Xi; Wen,Jia; Liu,Chaoqi; Guo,Donggeng

doi:10.3892/mmr.2022.12680

KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS‑induced ATDC5 cells via SIRT1/NF‑κB/p53 signaling

Authors:
- Xi Chen
- Jia Wen
- Chaoqi Liu
- Donggeng Guo
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Affiliations: Rheumatology and Immunology Department, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750000, P.R. China, Journal of Modern Clinical Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750000, P.R. China, Central Laboratory, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750000, P.R. China
Published online on: March 14, 2022 https://doi.org/10.3892/mmr.2022.12680
Article Number: 164
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease. Transcriptional regulation of fibroblast growth factor 21 (FGF21) by the transcription factor Krüppel‑like factor 4 (KLF4) serves an important role in chronic inflammatory disease. However, to the best of our knowledge, the role of both these factors in AS has not been previously reported. In the present study, ATDC5 cells were induced by lipopolysaccharide (LPS) to establish an AS inflammatory injury model. The expression levels of FGF21 and KLF4 were detected using reverse transcription‑quantitative PCR and western blotting. Cell transfection was performed to alter the expression levels of KLF4 and FGF21. Subsequently, the regulatory effects and mechanisms underlying KLF4 and FGF21 on oxidative stress and inflammation in AS were investigated by performing Cell Counting Kit‑8 assays, ELISAs, TUNEL staining and western blotting. Moreover, the expression levels of sirtuin 1 (SIRT1)/NF‑κB/p53 pathway‑related proteins were detected via western blotting. FGF21 overexpression promoted LPS‑induced viability on ATDC5 cells, inhibited LPS‑induced apoptosis, and decreased the LPS‑induced inflammatory response and oxidative stress levels of ATDC5 cells. Overexpression of the transcription factor KLF4 reversed the protective effect of FGF21 overexpression on LPS‑induced inflammatory injury in ATDC5 cells. The results suggested that this process may be achieved via regulating the SIRT1/NF‑κB/p53 signaling pathway. Overall, the present study demonstrated that KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS‑induced ATDC5 cells via SIRT1/NF‑κB/p53 signaling.

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