miR-29b-3p protects cardiomyocytes against endotoxin-induced apoptosis and inflammatory response through targeting FOXO3A
miR-29b-3p protects cardiomyocytes against endotoxin-induced apoptosis and inflammatory response through targeting FOXO3A
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miR-29b-3p 通过靶向 FOXO3A 保护心肌细胞免受内毒素诱导的细胞凋亡和炎症反应
DOI：
10.1016/j.cellsig.2020.109716
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发表时间：
2020-10-01
影响因子：
4.8
通讯作者：
Peng, Luying
中科院分区：
文献类型：
--
作者：
Li, Zhigang;Yi, Na;Peng, Luying
心功能不全是重症监护病房脓毒症引起死亡的主要组成部分。microRNAs（miRNAs）是脓毒症的重要调节因子或生物标志物。然而，参与脓毒性心功能不全的miRNAs的分子细节仍不清楚。在这里，我们发现内毒素（脂多糖，LPS）显着下调心脏中miR-29 b-3 p的表达。慢病毒介导的miR-29 b-3 p表达上调可改善小鼠心功能，减轻LPS诱导的心脏损伤。此外，miR-29 b-3 p的过表达或敲低显示其通过直接靶向FOXO 3A在NRCM中调节细胞凋亡和促炎细胞因子的产生中起关键作用。miR 29 B-3 p可能通过减少MAPK的活化和NF-κ B的核转位以阻断LPS活化的NF-κ B信号传导来改善炎性损伤。值得注意的是，与正常受试者相比，败血症患者血浆中的miR-29 b也下调，表明miR-29 b的潜在临床相关性。综上所述，我们的研究结果表明，上调miR-29 b-3 p可以通过调节FOXO 3A减轻脓毒症诱导的心肌损伤，这为干预脓毒症心功能障碍提供了潜在的治疗靶点。
Cardiac dysfunction represents a main component of death induced by sepsis in critical care units. And microRNAs (miRNAs) have been reported as important modulators or biomarkers of sepsis. However, the molecular detail of miRNAs involved in septic cardiac dysfunction remains unclear. Here we showed that endotoxin (lipopolysaccharide, LPS) significantly down-regulated expression of miR-29b-3p in heart. Increased expression of miR-29b-3p by lentivirus improved cardiac function and attenuated damage of cardiac induced by LPS in mice. Furthermore, overexpression or knockdown of miR-29b-3p showed its crucial roles on regulation of apoptosis and production of pro-inflammatory cytokines in NRCMs through directly targeting FOXO3A. miR29b-3p ameliorates inflammatory damage likely via reducing activation of MAPKs and nuclear-translocation of NF-kappa B to block LPS-activated NF-kappa B signaling. Notably, miR-29b is also down-regulated in septic patients' plasma compared with normal subjects, indicating a potential clinical relevance of miR-29b. Taken together, our findings demonstrate that upregulation of miR-29b-3p can attenuate myocardial injury induced by sepsis via regulating FOXO3A, which provide a potential therapy target for interference of septic cardiac dysfunction.