Upregulation of FABP7 inhibits acute kidney injury-induced TCMK-1 cell apoptosis via activating the PPAR gamma signalling pathway?

Molecular Omics Pub Date: 2020-08-13 DOI: 10.1039/D0MO00056F

Abstract

Acute kidney injury (AKI) is a frequently seen critical disorder in the clinic. The current research aimed to examine the role of hydroxyacid oxidase 2 (FABP7) in AKI-induced cell apoptosis. A total of 289 overlapping genes were used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and to construct a protein–protein interaction (PPI) network using the DAVID database and Cytoscape software. The 10 hub genes of the PPI network were screened out using the cytohubba plug-in of Cytoscape software. FABP7 represented both the differentially expressed gene (DEG) from the GSE44925 and GSE62732 datasets and the top hub gene of the PPI network. The results of the PAS assay showed that FABP7 knockout in vivo aggravated lipopolysaccharide (LPS)-induced AKI. Meanwhile, LPS inhibited cell viability and the expression of FABP7, PPARγ, PPARα, PTEN and p27kip1, and increased the TNF-α level, and cleaved caspase-3/-9 expression and the phosphorylation of PTEN in vitro. FABP7 overexpression reversed the effects of LPS on inhibiting cell viability and proliferation, promoting cell apoptosis, increasing the expression of FABP7, PPARγ, PTEN and p27kip1, and reducing cleaved caspase-3/-9 expression and the phosphorylation of PTEN, but had no influence on PPARα expression. The PPARγ signal pathway inhibitors blocked the protective effect of FABP7 overexpression in LPS-treated TCMK-1 cells, while the PPARγ signal pathway activator inhibited the harmful effect of FABP7 inhibition in LPS-treated TCMK-1 cells. In conclusion, FABP7 overexpression inhibited the AKI-induced cell apoptosis and promoted the proliferation through activating the PPARγ signal pathway in vivo and in vitro.

Graphical abstract: Upregulation of FABP7 inhibits acute kidney injury-induced TCMK-1 cell apoptosis via activating the PPAR gamma signalling pathway
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