Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 101, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107592
Keywords
Myocardial ischemia-reperfusion injury; Bone marrow mesenchymal stem cell; Exosome; MicroRNA-98-5p; Toll-like receptor 4; Phosphatidylinositol-3-kinase/protein kinase B signaling pathway
Categories
Ask authors/readers for more resources
Exosomal miR-98-5p derived from hypoxia-induced BMSCs protects against myocardial ischemia-reperfusion injury by promoting cardiac function, suppressing inflammation response and oxidative stress, and targeting TLR4 to activate the PI3K/Akt signaling pathway.
Objective: MicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia-reperfusion injury (MI/RI). Methods: BMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. Results: MiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. Conclusion: Hypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available