Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (9): 57-68.doi: 10.6040/j.issn.1671-7554.0.2023.0427

• Preclinical Medicine • Previous Articles     Next Articles

Bioinformatics identification of the Hub genes and mechanism of hypoxia-induced mitochondrial damage in mouse kidney

GAO Yujie, LONG Qifu, HU Ying, XU Yuzhen, WANG Ru, YONG Sheng   

  1. Department of Basic Medicine, College of Medicine, Qinghai University, Xining 810016, Qinghai, China
  • Received:2023-05-22 Published:2023-10-10

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Abstract: Objective To explore the Hub genes of hypoxia-induced mitochondrial damage by bioinformatics analysis, and to analyze the correlation between hub genes and apoptosis of mouse kidney tissue, so as to elucidate the molecular mechanism of hypoxia-induced mitochondrial damage in mice at high altitude. Methods After animal models of 30 d normoxicity group(n=5)and hypoxia group(n=5)were established, blood gas and renal indexes were determined. Histopathological changes of renal tissues were observed with H&E staining, and transcriptomics sequencing was performed. The differentially expressed genes(DEGs)were correlated with mitochondrial database and apoptosis-related gene database to identify DEGs related to mitochondrial function(DE-MFRGs)and DEGs related to apoptosis(DE-ARGs), and to screen Hub genes for protein-protein interaction(PPI). KEGG enrichment analysis was conducted on DEGs, DE-MFRGs and DE-ARGs. Hub genes and DE-ARGs were verified with RT-qPCR and Western blotting. Results Compared with the normoxicity group, the hypoxia group had significantly decreased kidney indexes. H&E staining results showed that the glomeruli in the hypoxia group were significantly atrophied; the renal tubule epithelial cells were swollen, ruptured, or infiltrated by inflammatory cells; the volume of some renal tubule epithelial cells was increased; the cytoplasm was loose and light stained, with cavitation degeneration. A total of 3,007 DEGs were identified under hypoxic exposure, among which 464 were related to mitochondrial function and were defined as DE-MFRGs. KEGG enrichment analysis of DE-MFRGs showed that they were involved with Parkinsons disease signaling pathway, oxidative phosphorylation signaling pathway, thermogenesis signaling pathway, Alzheimers disease signaling pathway, tricarboxylic acid cycling signaling pathway, NAFLD signaling pathway, metabolic signaling pathway and other pathways related to mitochondrial function. Three Hub genes(SOD2, TUFM and MRPL12)were identified through the construction of PPI network. The mRNA and protein expressions of SOD2, TUFM and MRPL12 were down-regulated. Furthermore, Hub genes were positively or negatively correlated with 33 ARGs genes, and the mRNA expression of CASPASE3 and BAK were up-regulated, while that of BCL2 was down-regulated. Conclusion The high altitude hypoxia environment can regulate the mRNA expressions of SOD2, TUFM and MRPL12, mediate the mitochondrial dysfunction of mouse kidney tissue, and induce damage and apoptosis.

Key words: Plateau hypoxia, Kidney, Mitochondrial function, Hub gene, Apoptosis, Mitochondrial database

CLC Number: 

  • R34
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