Open Access

Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease

  • Authors:
    • Fangyou Lin
    • Lei Xu
    • Run Yuan
    • Shangting Han
    • Jinna Xie
    • Kun Jiang
    • Bojun Li
    • Weimin Yu
    • Ting Rao
    • Xiangjun Zhou
    • Fan Cheng
  • View Affiliations

  • Published online on: January 19, 2022     https://doi.org/10.3892/ijmm.2022.5087
  • Article Number: 32
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

An increasing number of inflammatory responses and alternative splicing (AS) have been recently reported to be associated with various kidney diseases. The effect of inflammatory response on acute kidney injury (AKI) has not been fully clarified. In the present study, a mouse model of AKI induced by cisplatin and ischemia‑reperfusion (IR) was established and genome‑wide profiling analysis and identification of differentially expressed genes (DEGs) in kidney tissue was conducted by Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein‑protein interaction (PPI) network analysis and RT‑qPCR. The results revealed that common DEGs in AKI induced by cisplatin and IR were enriched in the inflammatory response pathway, including hub genes CSF‑1, CXCL1, CXCL10, IL‑1β, IL‑34, IL‑6 and TLR2. AS in AKI was initially reported. Cisplatin‑induced AS was enriched in the phosphorylation pathway, involving regulated AS genes CSNK1A1, PAK2, CRK, ADK and IKBKB. IR‑induced AS was enriched in apoptosis and proliferation pathways, including DEGs ZDHHC16, BCL2L1 and FGF1 regulated by AS. The ability of RNA‑binding proteins (RBPs) to regulate AS was coordinated with the function of context‑dependent genetic mechanisms. A total of 49 common differentially expressed RBP genes were screened. RNA binding fox‑1 homolog 1 (RBFOX1) was revealed to be the top downregulated gene. The relative levels of RBFOX1 in the nuclei of mouse renal tubular epithelial cells in mRNA and proteins were downregulated by cisplatin and IR. Moreover, the biological functions of RBFOX1 were investigated in human renal proximal tubular epithelial cells (HK‑2 cells). Results of in vitro experiments revealed that exogenous RBFOX1 inhibited inflammation and oxidative stress to reduce hypoxia/reoxygenation‑induced apoptosis of HK‑2 cells. This phenomenon may be related to the inhibition of NF‑κB and the activation of the NRF2/HO‑1 signaling pathway. In conclusion, the inflammatory cytokines, AS and RBPs in AKI were analyzed in the present study via whole transcriptome sequencing. It was revealed that the RBP gene RBFOX1 was involved in the pathogenesis of AKI. Thus, the present study provided novel insights into the mechanism of AKI pathogenesis.
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March-2022
Volume 49 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lin F, Xu L, Yuan R, Han S, Xie J, Jiang K, Li B, Yu W, Rao T, Zhou X, Zhou X, et al: Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease. Int J Mol Med 49: 32, 2022.
APA
Lin, F., Xu, L., Yuan, R., Han, S., Xie, J., Jiang, K. ... Cheng, F. (2022). Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease. International Journal of Molecular Medicine, 49, 32. https://doi.org/10.3892/ijmm.2022.5087
MLA
Lin, F., Xu, L., Yuan, R., Han, S., Xie, J., Jiang, K., Li, B., Yu, W., Rao, T., Zhou, X., Cheng, F."Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease". International Journal of Molecular Medicine 49.3 (2022): 32.
Chicago
Lin, F., Xu, L., Yuan, R., Han, S., Xie, J., Jiang, K., Li, B., Yu, W., Rao, T., Zhou, X., Cheng, F."Identification of inflammatory response and alternative splicing in acute kidney injury and experimental verification of the involvement of RNA‑binding protein RBFOX1 in this disease". International Journal of Molecular Medicine 49, no. 3 (2022): 32. https://doi.org/10.3892/ijmm.2022.5087