MiR-21-5p-expressing bone marrow mesenchymal stem cells alleviate myocardial ischemia/reperfusion injury by regulating the circRNA_0031672/miR-21-5p/programmed cell death protein 4 pathway
Jing ZHANG1
Chang-Jun LUO1
Xiao-Qi XIONG1
Jun LI1
San-Hua TANG1
Lin SUN2
Qiang SU3
1.Department of Cardiovascular Medicine,Liuzhou Municipal Liutie Central Hospital,Liuzhou,China2.Department of Clinical Laboratory,Liuzhou Municipal Liutie Central Hospital,Liuzhou,China3.Department of Cardiology,Affiliated Hospital of Guilin Medical University,Guangxi,China
摘要：BACKGROUND For patients with coronary heart disease, reperfusion treatment strategies are often complicated by ischemia/reperfusion (I/R) injury (IRI), leading to serious organ damage and malfunction. The miR-21/programmed cell death protein 4 (PDCD4) pathway is involved in the IRI of cardiomyocytes; however, the aberrant miR-21 expression remains unexplained. Therefore, this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to dete-rmine whether miR-21-5p-expressing bone marrow mesenchymal stem cells (BMSCs) reduce myocardial IRI. METHODS CircRNA_0031672, miR-21-5p, and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxy-genation (H/R)-treated H9C2 cells. Their interactions were subsequently investigated using luciferase reporter and RNA pull-down assays. Methyltransferase-like 3, a methyltransferase catalyzing N6-methyladenosine (m6A), was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4. BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R. RESULTS I/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions. CircRNA_0031672 knockdown increased miR-21-5p expression, but repressed PDCD4 expression, indicating that circRNA_0031672 com-petitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA. The m6A modification regulated PDCD4 expres-sion, but had no effect on miR-21-5p targeting PDCD4. The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment; co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R. CONCLUSIONS We identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs, offering novel insights into the IRI pathogenesis in cardiovascular diseases.
机标关键词：ischemiapathwayproteinstemcellsalleviatebonecircrna_0031672
论文发表日期：2021-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：15( 1029-1043 )