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miR-29b-3p protects cardiomyocytes against endotoxin-induced apoptosis and inflammatory response through targeting FOXO3A.
Cellular Signalling ( IF 4.4 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.cellsig.2020.109716
Zhigang Li 1 , Na Yi 1 , Rou Chen 2 , Yilei Meng 1 , Yumei Wang 2 , Huan Liu 1 , Wenze Cao 1 , Yi Hu 1 , Yanqiong Gu 3 , Chang Tong 4 , Min Lu 4 , Li Li 5 , Luying Peng 5
Affiliation  

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. miR-29b-3p ameliorates inflammatory damage likely via reducing activation of MAPKs and nuclear-translocation of NF-κB to block LPS-activated NF-κB 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.



中文翻译:

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。

心脏功能障碍是重症监护病房脓毒症所致死亡的主要组成部分。并且 microRNA (miRNA) 已被报道为败血症的重要调节剂或生物标志物。然而,参与败血性心脏功能障碍的 miRNA 的分子细节仍不清楚。在这里,我们发现内毒素(脂多糖,LPS)显着下调了心脏中 miR-29b-3p 的表达。慢病毒增加 miR-29b-3p 的表达可改善小鼠的心脏功能并减轻 LPS 诱导的心脏损伤。此外,miR-29b-3p的过表达或敲低显示其通过直接靶向FOXO3A在NRCMs中调节细胞凋亡和促炎细胞因子的产生中的关键作用。miR-29b-3p 可能通过减少 MAPK 的激活和 NF-κB 的核易位以阻断 LPS 激活的 NF-κB 信号传导来改善炎症损伤。值得注意的是,与正常受试者相比,脓毒症患者血浆中的 miR-29b 也下调,表明 miR-29b 具有潜在的临床相关性。总之,我们的研究结果表明,miR-29b-3p 的上调可以通过调节 FOXO3A 来减轻脓毒症诱导的心肌损伤,这为干扰脓毒症心功能障碍提供了潜在的治疗靶点。

更新日期:2020-07-29
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