microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis.
microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis.
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microRNA-124-3p 通过调节 SP1/HDAC4/HIF-1α 轴减轻脓毒症心肌损伤
DOI：
10.1038/s41420-021-00763-y
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发表时间：
2022-01-28
影响因子：
7
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Wu M;Huang Z;Huang W;Lin M;Liu W;Liu K;Li C
脓毒症诱导的心脏功能障碍可导致脓毒症患者死亡。在此情况下，我们旨在通过特异性蛋白1/组蛋白去乙酰化酶4/缺氧诱导因子1α（SP1/HDAC4/HIF - 1α）轴详细探究微小RNA（miR）- 124 - 3p在脓毒症诱导的心肌损伤中的相关机制。通过盲肠结扎穿孔法建立脓毒症大鼠模型，同时用脂多糖（LPS）诱导体外培养的脓毒症心肌细胞H9C2。检测脓毒症大鼠心肌组织以及LPS处理的H9C2细胞中miR - 124 - 3p/SP1/HDAC4/HIF - 1α的表达水平。在LPS处理的H9C2细胞上进行miR - 124 - 3p过表达和SP1沉默实验，以探究它们在炎症、氧化应激和细胞凋亡中的作用。验证了miR - 124 - 3p、SP1和HDAC4之间的相互作用。在脓毒症中，miR - 124 - 3p表达较低，而SP1、HDAC4和HIF - 1α表达较高。miR - 124 - 3p的上调可改善LPS处理的H9C2细胞的炎症、氧化应激和凋亡。沉默SP1可改善LPS对心肌细胞造成的损伤。miR - 124 - 3p靶向SP1，且HDAC4与SP1相互作用。SP1过表达可拮抗miR - 124 - 3p上调对LPS诱导的心肌细胞损伤的改善作用。本研究表明，miR - 124 - 3p通过靶向调控SP1介导HDAC4/HIF - 1α来改善脓毒症大鼠的心肌损伤。
Sepsis-induced cardiac dysfunction can lead to death in sepsis. In this case, we targeted to explore in detail the relative mechanism of microRNA (miR)-124-3p in sepsis-induced myocardial injury via the specific protein 1/histone deacetylase 4/hypoxia-inducing factor 1α (SP1/HDAC4/HIF-1α) axis. Septic rats were modeled by cecal ligation puncture while in vitro septic cardiomyocyte H9C2 were induced by lipopolysaccharide (LPS). miR-124-3p/SP1/HDAC4/HIF-1α expression levels in myocardial tissues of septic rats and LPS-treated H9C2 cells were measured. miR-124-3p overexpression and SP1 silencing assays were implemented on LPS-treated H9C2 cells to explore theirs actions in inflammation, oxidative stress and cell apoptosis. The interactions of miR-124-3p, SP1, and HDAC4 were testified. miR-124-3p was lowly expressed while SP1, HDAC4, and HIF-1α were highly expressed in sepsis. Upregulation of miR-124-3p ameliorated inflammation, oxidative stress, and apoptosis of LPS-treated H9C2 cells. Silencing SP1 improved LPS-induced damage to cardiomyocytes. miR-124-3p targeted SP1 and HDAC4 interacted with SP1. SP1 overexpression antagonized miR-124-3p upregulation-induced improvements in LPS-induced cardiomyocyte damage. This study illustrates that miR-124-3p improves myocardial injury in septic rats through targeted regulation of SP1 to mediate HDAC4/HIF-1α.
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