Wu Lizhou, Li Zhan, Song Wenhui, Zhang Li, Li Kuan, Wang Haiyan
Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, China.
Sci Rep. 2025 Apr 30;15(1):15213. doi: 10.1038/s41598-025-00104-4.
Cardiac shock wave therapy (CSWT) as an effectual therapy can activate the function of exosomes to a certain extent. Here, we attempted to examine the role of CSWT in exosome released from ischemic cardiomyocytes and its function in myocardial ischemia recovery. The exosomes derived from OGD/R-treated H9c2 (H9c2-OGD/R-Exo) and CSWT-treated OGD/R-stimulated H9c2 (CSWT-H9c2-OGD/R-Exo) were performed with small RNA sequencing to determine miRNAs that differentially expressed. After miR-98-5p inhibitor transfection, H9c2 were subjected to OGD/R and co-cultured with CSWT-H9c2-OGD/R-Exo, the cell viability, LDH and cell apoptosis were assessed. The transfected HUVECs were co-cultured with CSWT-H9c2-OGD/R-Exo, then HUVECs viability, angiogenesis, migration and invasion were assessed. The luciferase reporter gene assay was conducted to prove the targeting relation between miR-98-5p and FOXN3. miR-98-5p was highly enriched in CSWT-H9c2-OGD/R-Exo in compared with H9c2-OGD/R-Exo. CSWT-H9c2-OGD/R-Exo could improve cell viability, inhibit LDH and cell apoptosis. And miR-98-5p released by CSWT-H9c2-OGD/R-Exo promoted HUVECs viability, angiogenesis, migration and invasion. Further FOXN3 was defined as the downstream target gene of miR-98-5p, and miR-98-5p overexpression decreased FOXN3 expression in HUVECs. Besides, the suppression effects of miR-98-5p inhibitor on HUVECs proliferation, angiogenesis and metastasis was partly blunted by FOXN3 silencing. miR-98-5p released from CSWT-H9c2-OGD/R-Exo promoted HUVECs proliferation, angiogenesis and metastasis through directly targeting and suppressing FOXN3 expression.
心脏冲击波疗法（CSWT）作为一种有效的治疗方法，在一定程度上可以激活外泌体的功能。在此，我们试图研究CSWT在缺血心肌细胞释放的外泌体中的作用及其在心肌缺血恢复中的功能。对源自氧糖剥夺/复氧（OGD/R）处理的H9c2细胞的外泌体（H9c2-OGD/R-Exo）和经CSWT处理的OGD/R刺激的H9c2细胞的外泌体（CSWT-H9c2-OGD/R-Exo）进行小RNA测序，以确定差异表达的微小RNA（miRNA）。在转染miR-98-5p抑制剂后，将H9c2细胞进行OGD/R处理，并与CSWT-H9c2-OGD/R-Exo共培养，评估细胞活力、乳酸脱氢酶（LDH）水平和细胞凋亡情况。将转染后的人脐静脉内皮细胞（HUVECs）与CSWT-H9c2-OGD/R-Exo共培养，然后评估HUVECs的活力、血管生成、迁移和侵袭能力。进行荧光素酶报告基因检测以证实miR-98-5p与叉头框蛋白N3（FOXN3）之间的靶向关系。与H9c2-OGD/R-Exo相比，miR-98-5p在CSWT-H9c2-OGD/R-Exo中高度富集。CSWT-H9c2-OGD/R-Exo可以提高细胞活力，抑制LDH释放和细胞凋亡。并且CSWT-H9c2-OGD/R-Exo释放的miR-98-5p促进了HUVECs的活力、血管生成、迁移和侵袭。进一步确定FOXN3为miR-98-5p的下游靶基因，miR-98-5p过表达降低了HUVECs中FOXN3的表达。此外，FOXN3沉默部分减弱了miR-98-5p抑制剂对HUVECs增殖、血管生成和转移的抑制作用。CSWT-H9c2-OGD/R-Exo释放的miR-98-5p通过直接靶向并抑制FOXN3表达来促进HUVECs的增殖、血管生成和转移。
