Cardiac Fibroblast Activation Induced by Oxygen –Glucose Deprivation Depends on the HIF-1α/miR-212-5p/KLF4 Pathway

This study aimed to identify a new pathway of miR-212-5p in the activation of human cardiac fibroblasts (HCFs) induced by oxygen –glucose deprivation (OGD). First, we found that KLF4 protein was markedly decreased in OGD-induced HCFs. Then, bioinformatics analysis and verification experiments were used to identify the existence of an interaction of KLF4 with miR-212-5p. Functional experiments indicated that OGD significantl y upregulated the expression of hypoxia inducible factor-1 alpha (HIF-1 α) in HCFs, which positively regulated miR-212-5p transcription by binding to its promoter. MiR-212-5p inhibited the expression of Krüppel-like factor 4 (KLF4) protein by binding to the 3’ untranslated coding regions (UTRs) of KLF4 mRNA. Inhibition of miR-212-5p effectively inhibited the activat ion of OGD-induced HCFs by upregulating KLF4 expression and inhibited cardiac fibrosis in vivo and in vitro.Graphical Abstract
Source: Journal of Cardiovascular Translational Research - Category: Cardiology Source Type: research