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TCF4 通过转录调控 COX7A2L 促进急性肾损伤中的细胞凋亡和 Wnt/β-catenin 信号通路。

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

机构信息

Department of Nephrology, Shanghai Pudong New Area People's Hospital, Shanghai, China.

出版信息

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

DOI:10.1371/journal.pone.0307667
PMID:39499704
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11537394/
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.

摘要

背景

急性肾损伤（AKI）仍然是一种严重的肾脏疾病，具有较高的发病率和死亡率，因此了解其潜在的分子原因至关重要。

方法

对 GSE139061 和 GSE30718 数据集进行生物信息学分析，筛选出 COX7A2L。评估 COX7A2L 在 H/R 处理细胞中的作用及其与 TCF4 的转录调控。体外实验分析了 COX7A2L 和 TCF4 对 H/R 处理细胞增殖、凋亡和 Wnt/β-catenin 信号通路的调节作用。

结果

COX7A2L 作为一个枢纽基因在 AKI 样本中下调。在 H/R 处理的细胞中，过表达 COX7A2L 抑制细胞凋亡并促进细胞增殖，而敲低 COX7A2L 则促进细胞凋亡并抑制细胞增殖。值得注意的是，TCF4 与 COX7A2L 呈显著正相关。根据挽救研究的结果，TCF4 过表达诱导的细胞凋亡减少，而 COX7A2L 敲低则抵消了细胞增殖的改善。此外，我们发现 TCF4 过表达增加了与 Wnt/β-catenin 信号通路相关的蛋白表达（c-myc、β-catenin 和 cyclin D1），而 COX7A2L 的下调则抵消了这一效应。

结论

本研究揭示了 COX7A2L 在 AKI 中的关键作用，该作用受 TCF4 调节，并调节 Wnt/β-catenin 信号通路，强调了其作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/cc71c6f0ec77/pone.0307667.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/365c56c8d62a/pone.0307667.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/9c1adb8a4e34/pone.0307667.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/8b089d89b88d/pone.0307667.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/db61d8c358a6/pone.0307667.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/912c01d82823/pone.0307667.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/cc71c6f0ec77/pone.0307667.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/365c56c8d62a/pone.0307667.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/9c1adb8a4e34/pone.0307667.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/8b089d89b88d/pone.0307667.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/db61d8c358a6/pone.0307667.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/912c01d82823/pone.0307667.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e0a/11537394/cc71c6f0ec77/pone.0307667.g006.jpg

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