TCF4 promotes apoptosis and Wnt/β-catenin signaling pathway in acute kidney injury via transcriptional regulation of COX7A2L

PLoS One. 2024 Nov 5;19(11):e0307667. doi: 10.1371/journal.pone.0307667. eCollection 2024.

Abstract

Background: Acute kidney injury (AKI) is still a serious kidney illness with high morbidity and death rates, and it's crucial to comprehend the underlying molecular causes.

Methods: Bioinformatics analysis was performed on GSE139061 and GSE30718 data sets, and COX7A2L was screened out. The role of COX7A2L in H/R-treated cells and its transcriptional regulation with TCF4 were assessed. In vitro experiments analyzed the regulation of COX7A2L and TCF4 on the proliferation, apoptosis, and Wnt/β-catenin signaling pathway of H/R-treated cells.

Results: COX7A2L as a hub gene was downregulated in AKI samples. In H/R-treated cells, COX7A2L overexpression inhibited apoptosis and promoted cell proliferation, while COX7A2L knockdown promoted apoptosis and inhibited cell proliferation. Notably, TCF4 exhibited a significant positive correlation with COX7A2L. TCF4 overexpression-induced apoptosis was lessened and improved cell proliferation was countered by COX7A2L knockdown, according to rescue study findings. Besides, we discovered that TCF4 overexpression increased the expression of proteins linked to the Wnt/β-catenin signaling pathway (c-myc, β-catenin, and cyclin D1), while underexpression of COX7A2L counteracted this effect.

Conclusion: The study revealed the pivotal role of COX7A2L in AKI, which is regulated by TCF4 and modulates the Wnt/β-catenin signaling pathway, highlighting its potential as a therapeutic target.

MeSH terms

  • Acute Kidney Injury* / genetics
  • Acute Kidney Injury* / metabolism
  • Acute Kidney Injury* / pathology
  • Apoptosis* / genetics
  • Cell Proliferation* / genetics
  • Gene Expression Regulation
  • Humans
  • Transcription Factor 4* / genetics
  • Transcription Factor 4* / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Transcription Factor 4
  • TCF4 protein, human
  • beta Catenin