LncRNA HCP5 in hBMSC-derived exosomes alleviates myocardial ischemia reperfusion injury by sponging miR-497 to activate IGF1/PI3K/AKT pathway

Abstract

Ischemia/reperfusion (I/R) injury is an inevitable process during heart transplant and suppressing I/R injury could greatly improve the survival rate of recipients. Mesenchymal stem cells (MSCs) have positive effects on I/R. We aimed to investigate the mechanisms underlying the protective roles of MSCs in I/R. Both cell model and rat model of myocardial I/R were used. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. QRT-PCR and western blotting were employed to measure levels of lncRNA HCP5 (HLA complex P5), miR-497, apoptosis-related proteins, and insulin-like growth factor (IGF1)/PI3K/AKT pathway. Dual luciferase assay was used to validate interactions of HCP5 and miR-497, miR-497 and IGF1. Echocardiography was performed to evaluate cardiac function of rats. Serum levels of CK-MB and LDH were measured. H&E and Masson staining were used to examine morphology of myocardial tissues. hBMSC-derived exosomes (hBMSC-Exos) increased the viability of cardiomyocytes following hypoxia/reperfusion (H/R) and decreased apoptosis. H/R diminished HCP5 expression in cardiomyocytes while hBMSC-Exos recovered the level. Overexpression of HCP5 in hBMSC-Exos further enhanced the protective effects in H/R while HCP5 knockdown suppressed. HCP5 directly bound miR-497 and miR-497 targeted IGF1. miR-497 mimics or si-IGF1 blocked the effects of HCP5 overexpression. Further, hBMSC-Exos alleviated I/R injury in vivo and knockdown of HCP5 in hBMSC-Exos decreased the beneficial effects. AntagomiR-497 blocked the effects of HCP5 knockdown. HCP5 from hBMSC-Exos protects cardiomyocytes against I/R injury via sponging miR-497 to disinhibit IGF1/PI3K/AKT pathway. These results shed light on mechanisms underlying the protective role of hBMSC-Exos in I/R.

Analysis of the miRNA-mRNA Regulatory Network Reveals the Biomarker Genes in the Progression of Myocardial Ischemic Reperfusion

“…According to the abundance of the genes, IFG1 was identified as a target of mmu-miR-27b-3p. The study has indicated that IFG1 can reduce MI/R injury via activating the PI3K/AKT pathway [ 29 ]. Moreover, Chen et al indicated that upregulated miR-27b-3p could inhibit the progression of breast cancer via targeting the PI3K/AKT pathway [ 30 ].…”

Doxorubicin-Induced Cardiotoxicity May Be Alleviated by Bone Marrow Mesenchymal Stem Cell-Derived Exosomal lncRNA via Inhibiting Inflammation

“…22,23 Long noncoding RNAs (lncRNAs) have been involved in the apoptosis, 24 proliferation or regeneration of cardiomyocyte. [25][26][27] Moreover, lncRNAs in exosomes have been shown to be involved in the inhibition of cardiomyocyte apoptosis 28,29 and pyroptosis. 30 In this study, we constructed DIC model in vitro firstly.…”

Advances in lncRNAs from stem cell-derived exosome for the treatment of cardiovascular diseases

“…An increase of miR-497 during ischemia-reperfusion (I/R) injury may cause cardiomyocyte apoptosis. Li et al ( Li K.-S. et al, 2021 ) confirmed that Introducing Exo-lncRNA-HCP5 in hBMSCs into cardiomyocytes can protect cardiomyocytes from injury via the miR-497↓/insulin like growth factor-1 (IGF-1)/phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT)↓ signal pathway. Meanwhile, Zhang et al ( Zhang J.-K. et al, 2022 ) treated HL-1 mouse cardiomyocytes and myocardial tissue of hypoxia reperfusion (H/R) myocardial cells ferroptosis mouse model with BMSCs-Exo-lncRNA-Mir9-3hg.…”