Department of Critical Care Medicine, Affiliated Hospital of Putian University, Putian 351100, Fujian, China.
Department of Critical Care Medicine, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian, China.
Aging (Albany NY). 2021 Sep 16;13(18):22276-22285. doi: 10.18632/aging.203533.
The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported.
Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound heating, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes.
Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR-497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs.
We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.
骨髓间充质干细胞（MSCs）分泌的细胞外囊泡（EVs）具有改善心肌梗死（MI）的能力。一些 microRNAs（miRNAs），包括 miR-497 和相关靶基因，已被证明与心脏病密切相关。然而，EVs 可以通过 miR-497 调节 MI 过程，但其机制尚未完全报道。
结扎左前降支建立 MI 动物模型。通过降低氧水平建立缺氧细胞模型。通过 transwell、伤口加热和 MTT 测定法测量细胞侵袭、迁移和增殖。HE、Masson 三色和 Sirius Red 染色用于研究形态变化。
miR-497 的过表达逆转了 EVs 引起的细胞迁移、侵袭和增殖的促进作用。EVs 诱导的心脏功能改善也可以通过 miR-497 的过表达来逆转。鉴定了 Smad7 和 miR-497 之间的直接结合位点。Smad7 的敲低逆转了 EVs 诱导的心脏功能改善。
我们发现，MSCs 分离的 EVs 可能通过靶向 miR497/Smad7 改善由 MI 引起的心脏损伤。这项研究为通过靶向 miR-497/Smad7 预防和治疗 MI 提供了新的潜在治疗思路。
