miRNA-146a-5p Inhibits Hypoxia-Induced Myocardial Fibrosis Through EndMT.

Abstract

Cardiac Vascular disease particularly myocardial infarction (MI) is a threat to health worldwide. microRNAs (miRNAs) have been shown to regulate myocardial fibrosis. Therefore, it is potential to investigate the mechanism of miRNA and fibrosis following myocardial infarction. Hypoxia human cardiac microvascular endothelial cells (HCMECs) were selected for the vitro experimental model. The miR-146a-5p expression was tested via RT-qPCR. The level of endothelial-to-mesenchymal transition (EndMT) and fibrosis markers were detected by Western blotting and immunofluorescence. Then, the inflammation, cell viability and apoptosis were investigated. The target was predicted by an online database and verified by a dual-luciferase activity assay. An MI mouse model was created to validate that miR-146a-5p regulates cardiac fibrosis in vivo. MI mouse was transfected with miR-146a-5p lentivirus. Subsequently, its effect on cardiac fibrosis of infarcted hearts was assessed by In situ hybridization (ISH), Immunohistochemistry (IHC), Triphenylterazolium chloride (TTC) staining and Masson staining. Herein, we confirmed that miR-146a-5p was down-regulated in hypoxia HCMECs. Overexpression of miR-146a-5p inhibited hypoxia-induced cardiac fibrosis following myocardial infarction by inhibiting EndMT in HCMECs. Thioredoxin-interacting protein (TXNIP) was a target that was negatively regulated by miR-146a-5p. Up-regulation of miR-146a-5p inhibited cardiac fibrosis via regulating EndMT by targeting TXNIP, and it also regulated EndMT to inhibit cardiac fibrosis in vivo.

• Authors: Yan Wang, Jie Yu, Chunxia Ou, Yue Zhao, Lixing Chen, Wenke Cai, Huawei Wang, Shiying Huang, Jie Hu, Guihu Sun, Longjun Li
• Journal: Cardiovascular toxicology (Cardiovasc Toxicol) Vol. 24 Issue 2 Pg. 133-145 (Feb 2024) ISSN: 1559-0259 [Electronic] United States
• PMID: 38180639 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• MicroRNAs

Topics

• Humans
• Mice
• Animals
• Endothelial Cells
• Endothelial-Mesenchymal Transition
• Fibrosis
• MicroRNAs (genetics, metabolism)
• Cardiomyopathies (metabolism)
• Myocardial Infarction (genetics, prevention & control, metabolism)
• Hypoxia (complications, genetics)
• Apoptosis