Department of Emergency, First Affiliated Hospital of Soochow University, Suzhou City 215000, China; Department of Emergency Medicine, Affiliated Hospital of Nantong University, Nantong City 226001, China.
Department of Trauma Center, Affiliated Hospital of Nantong University, No.20 Xisi Road, Chongchuan District, Nantong City, Jiangsu Province 226001, China.
Transpl Immunol. 2022 Feb;70:101493. doi: 10.1016/j.trim.2021.101493. Epub 2021 Nov 10.
Cardiac insufficiency is a common complication of sepsis and septic shock and is the most common cause of death in critically ill patients. Recent studies have found that microRNAs (miRNAs) play a potential role in sepsis as markers, but little is known about their functional effects on sepsis-induced cardiomyopathy (SIC).
This study is designed to explore the possible role and underlying mechanisms of miR-702-3p in septic cardiomyopathy.
As expected, H9c2 cells were induced with lipopolysaccharide (LPS) to construct the model of septic cardiomyopathy. The expression of miR-702-3p was detected by qRT-PCR assay and those of IL-1β, IL-6 and TNF-α by ELISA assay. The viability, proliferation and apoptosis of LPS-treated H9c2 cells were determined by CCK-8, EdU, flow cytometry and western blot assays. Moreover, Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) was predicted and confirmed as a direct target of miR-702-3p by TargetScan, miRwalk and miRDB prediction and dual-luciferase reporter gene assays.
While LPS can weaken the viability of H9c2 cells, miR-702-3p enhances that of LPS-treated H9c2 cells by inhibit the expressions of TNF-α, IL-6, IL-1β. We found NOD1 is a target gene of miR-702-3p, and over-expression of NOD1 restores the inhibitory effects of miR-702-3p on the LPS-treated H9c2 cells.
MiR-702-3p played an important role in the pathogenesis of sepsis cardiomyopathy via targeting NOD1, suggesting that miR-702-3p may be a potential new target for the treatment of SIC.
心功能不全是脓毒症和感染性休克的常见并发症，也是危重病患者死亡的最常见原因。最近的研究发现，微小 RNA（miRNA）作为标志物在脓毒症中发挥潜在作用，但它们对脓毒症性心肌病（SIC）的功能影响知之甚少。
本研究旨在探讨 miR-702-3p 在脓毒性心肌病中的可能作用及其潜在机制。
如预期的那样，用脂多糖（LPS）诱导 H9c2 细胞构建脓毒性心肌病模型。通过 qRT-PCR 检测 miR-702-3p 的表达，通过 ELISA 检测白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。通过 CCK-8、EdU、流式细胞术和 Western blot 检测 LPS 处理的 H9c2 细胞的活力、增殖和凋亡。此外，通过 TargetScan、miRwalk 和 miRDB 预测以及双荧光素酶报告基因检测，核苷酸结合寡聚化结构域蛋白 1（NOD1）被预测并确认为 miR-702-3p 的直接靶标。
LPS 可减弱 H9c2 细胞的活力，而 miR-702-3p 通过抑制 TNF-α、IL-6 和 IL-1β 的表达增强 LPS 处理的 H9c2 细胞的活力。我们发现 NOD1 是 miR-702-3p 的靶基因，过表达 NOD1 可恢复 miR-702-3p 对 LPS 处理的 H9c2 细胞的抑制作用。
miR-702-3p 通过靶向 NOD1 在脓毒症性心肌病发病机制中发挥重要作用，提示 miR-702-3p 可能是治疗 SIC 的潜在新靶点。
