阿霉素 (DOX) 是治疗血液肿瘤和乳腺癌的重要化疗药物。然而，由于严重的心脏毒性，其临床应用受到限制。细胞焦亡是一种程序性细胞死亡，与 DOX 诱导的心脏毒性有关。骨间充质干细胞衍生的外泌体 (BMSC-Exos) 和内皮祖细胞衍生的外泌体 (EPC-Exos) 对心肌具有保护作用。在这里，我们发现 BMSC-Exos 可以通过抑制细胞焦亡来改善 DOX 诱导的心脏毒性，但 EPC-Exos 则不能。与EPCs-Exo相比，BMSC-Exo过表达lncRNA GHET1更有效地抑制焦亡，防止DOX诱导的心脏毒性。进一步的研究表明，lncRNA GHET1 有效降低了 Nod 样受体蛋白 3 (NLRP3) 的表达，该蛋白通过与 IGF2 mRNA 结合蛋白 1 (IGF2BP1)（NLRP3 mRNA 的非催化转录后增强子）结合，在细胞焦亡中发挥着至关重要的作用。 。总之，BMSC-Exo 释放的 lncRNA GHET1 通过靶向 IGF2BP1 降低 NLRP3 的转录后稳定性，改善了 DOX 诱导的细胞焦亡。© 2024。作者。

Doxorubicin (DOX) is an important chemotherapeutic agent for the treatment of hematologic tumors and breast carcinoma. However, its clinical application is limited owing to severe cardiotoxicity. Pyroptosis is a form of programmed cell death linked to DOX-induced cardiotoxicity. Bone mesenchymal stem cell-derived exosomes (BMSC-Exos) and endothelial progenitor cells-derived exosomes (EPC-Exos) have a protective role in the myocardium. Here we found that BMSC-Exos could improve DOX-induced cardiotoxicity by inhibiting pyroptosis, but EPC-Exos couldn't. Compared with EPCs-Exo, BMSC-Exo-overexpressing lncRNA GHET1 more effectively suppressed pyroptosis, protecting against DOX-induced cardiotoxicity. Further studies showed that lncRNA GHET1 effectively decreased the expression of Nod-like receptor protein 3 (NLRP3), which plays a vital role in pyroptosis by binding to IGF2 mRNA-binding protein 1 (IGF2BP1), a non-catalytic posttranscriptional enhancer of NLRP3 mRNA. In summary, lncRNA GHET1 released by BMSC-Exo ameliorated DOX-induced pyroptosis by targeting IGF2BP1 to reduce posttranscriptional stabilization of NLRP3.© 2024. The Author(s).