1. Academic Validation
  2. Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-β/Smad2/3 axis activation

Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-β/Smad2/3 axis activation

  • Cell Cycle. 2021 May;20(9):874-893. doi: 10.1080/15384101.2021.1907512.
Zhen Tian 1 Yan Zhang 2 Xueman Lyu 3
Affiliations

Affiliations

  • 1 Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, Jilin, P. R. China.
  • 2 Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130031, Jilin, P. R.China.
  • 3 Department of Ophthalmology, China-Japan Union Hospital of Jilin University, Changchun 130031, Jilin, P. R.China.
Abstract

Myocardial infarction (MI) is a major atherosclerotic Cardiovascular Disease which represents a leading cause of death worldwide. Kruppel-like factor 5 (KLF5) is a member of the kruppel-like transcription factor family which has been reported with pro-apoptotic functions in myocardial cells. This work focuses on the function of KLF5 in the pathogenesis of MI and the molecules involved. A mouse model with MI was established. Hypoxia/reoxygenation (H/R)-treated H9C2 cells were applied for in vitro experiments. A KLF5-specific inhibitor ML264 was administrated in cell and animal models. ML264 significantly reduced Apoptosis, expression of fibrosis-related markers, Reactive Oxygen Species in the H/R-treated H9C2 cells, and it reduced myocardial injury, infarct size, Apoptosis and fibrosis in the myocardial tissues in model mice through specific downregulation of KLF5. A MicroRNA (miRNA) microarray analysis was performed, which suggested miR-27a as the most upregulated miRNA in the H/R-treated cells after ML264 treatment. miR-27a mimic reduced Apoptosis and fibrosis in H/R-treated cells, while miR-27a inhibition blocked the protective roles of ML264. The integrated bioinformatic analyses and luciferase assays confirmed glutamine fructose-6-phosphate transaminase 2 (GFPT2) mRNA as a target of miR-27a. Overexpression of GFPT2 counteracted the protective functions of miR-27a against MI through the activation of the TGF-β/SMAD2/3 signaling pathway. To conclude, this study evidenced that KLF5 possibly induces cell and tissue damage in MI through downregulation of miR-27a and the subsequent activation of GFPT2/TGF-β/SMAD2/3 axis. This study may offer novel thoughts into MI treatment.

Keywords

GFPT2; KLF5; Myocardial infarction; TGF-β/Smad2/3 signaling pathway; miR-27a; myocardial fibrosis.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19994
    99.21%, KLF5 Inhibitor
    KLF