AIM Myocardial infarction (MI) is a severe disease with increased mortality and disability rates, posing heavy economic burden for society. Exosomes were uncovered to mediate intercellular communication after MI. This study aims to explore the effect and mechanism of lncRNA KLF3-AS1 in exosomes secreted by human mesenchymal stem cells (hMSCs) on pyroptosis of cardiomyocytes and MI. METHODS Exosomes from hMSCs were isolated and identified. Exosomes from hMSCs with transfection of KLF3-AS1 for overexpression were injected into MI rat model or incubated with hypoxia cardiomyocytes. Effect of KLF3-AS1 on MI area, cell viability, apoptosis, and pyroptosis was determined. The relationship among miR-138-5p, KLF3-AS1, and Sirt1 was verified by dual-luciferase reporter assay. Normal cardiomyocytes were transfected with miR-138-5p inhibitor or sh-Sirt1 to clarify whether alteration of miR-138-5p or sh-Sirt1 can regulate the effect of KLF3-AS1 on cardiomyocytes. RESULTS Exosomes from hMSCs were successfully extracted. Transfection of KLF3-AS1 exosome in rats and incubation with KLF3-AS1 exosome in hypoxia cardiomyocytes both verified that overexpression of KLF3-AS1 in exosomes leads to reduced MI area, decreased cell apoptosis and pyroptosis, and attenuated MI progression. KLF3-AS1 can sponge miR-138-5p to regulate Sirt1 expression. miR-138-5p inhibitor transfection and KLF3-AS1 exosome incubation contribute to attenuated pyroptosis and MI both in vivo and in vitro, while transfection of sh-Sirt1 could reverse the protective effect of exosomal KLF3-AS1 on hypoxia cardiomyocytes. CONCLUSION LncRNA KLF3-AS1 in exosomes secreted from hMSCs by acting as a ceRNA to sponge miR-138-5p can regulate Sirt1 so as to inhibit cell pyroptosis and attenuate MI progression.

中文翻译：

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人间充质干细胞来源的外泌体中的LncRNA KLF3-AS1通过miR-138-5p / Sirt1轴改善了心肌细胞的热凋亡和心肌梗塞。

AIM心肌梗塞（MI）是一种严重的疾病，死亡率和致残率增加，给社会造成沉重的经济负担。MI后发现外泌体介导细胞间通讯。本研究旨在探讨人间充质干细胞（hMSCs）分泌的外泌体中lncRNA KLF3-AS1对心肌细胞和MI的热凋亡的作用及其机制。方法分离鉴定hMSCs的外泌体。将转染了KLF3-AS1的hMSC的外泌体用于过度表达，将其外泌体注射入MI大鼠模型或与缺氧心肌细胞一起孵育。确定了KLF3-AS1对心肌梗死面积，细胞活力，凋亡和凋亡的影响。miR-138-5p，KLF3-AS1和Sirt1之间的关系已通过双重萤光素酶报告基因检测验证。用miR-138-5p抑制剂或sh-Sirt1转染正常的心肌细胞，以阐明miR-138-5p或sh-Sirt1的改变是否可以调节KLF3-AS1对心肌细胞的作用。结果成功地从人间充质干细胞中提取了外来体。在大鼠中转染KLF3-AS1外泌体并在缺氧心肌细胞中与KLF3-AS1外泌体一起孵育均证实，外泌体中KLF3-AS1的过度表达可导致MI面积减少，细胞凋亡和发烧减少以及MI进展减缓。KLF3-AS1可以使miR-138-5p发挥作用，从而调节Sirt1的表达。miR-138-5p抑制剂的转染和KLF3-AS1外泌体的孵育在体内和体外均能减轻热病和心肌梗死，而转染sh-Sirt1可以逆转外泌体KLF3-AS1对缺氧心肌细胞的保护作用。