Diao Xiufang, Sun Shuqing
Department of Intensive Care Units, Weifang People's Hospital, Guangwen Road, Kuiwen District, Weifang City, Shandong Province, 261041, China.
Biotechnol Lett. 2017 Sep;39(9):1335-1342. doi: 10.1007/s10529-017-2368-4. Epub 2017 May 30.
To examine the role of miR-124a in LPS-induced septic cardiac insufficiency where underlying mechanism is unclear.
Expression of miR-124a was decreased in myocardium of LPS-induced septic cardiac dysfunction model. miR-124a antagomiR or agomiR were injected via tail vein to induce miR-124a-dysregulated model. miR-124a antagomiR aggravated LPS-induced cardiac dysfunction and apoptosis, while miR-124a agomiR had the opposite effect. Syntaxin-2 (STX2) was indicated as a candidate target gene by bioinformatic software. Further experiments confirmed that STX2 was downregulated in miR-124a agomiR-treated rats but upregulated in miR-124a antagomiR-treated rats, and STX2 inhibition could strongly block the miR-124a antagomiR-associated increase in cell apoptosis. Luciferase reporter activity assay indicated that STX2 was a direct target of miR-124a. Serological detection reveled that miR-124a was down-regulated in the plasma of septic cardiac dysfunction rats.
miR-124a aggravates LPS-induced cardiac dysfunction and the miR-124a/STX2 pathway might serve as the potential diagnostic and therapeutic targets for septic cardiac dysfunction.
探讨miR-124a在脂多糖(LPS)诱导的脓毒症性心功能不全中的作用,其潜在机制尚不清楚。
在LPS诱导的脓毒症性心脏功能障碍模型的心肌中,miR-124a的表达降低。通过尾静脉注射miR-124a拮抗剂或激动剂以诱导miR-124a失调模型。miR-124a拮抗剂加重了LPS诱导的心脏功能障碍和细胞凋亡,而miR-124a激动剂则具有相反的作用。生物信息学软件显示Syntaxin-2(STX2)为候选靶基因。进一步实验证实,在miR-124a激动剂处理的大鼠中STX2表达下调,而在miR-124a拮抗剂处理的大鼠中STX2表达上调,并且抑制STX2可强烈阻断miR-124a拮抗剂相关的细胞凋亡增加。荧光素酶报告基因活性测定表明STX2是miR-124a的直接靶标。血清学检测显示,脓毒症性心脏功能障碍大鼠血浆中miR-124a下调。
miR-124a加重LPS诱导的心脏功能障碍,miR-124a/STX2通路可能是脓毒症性心脏功能障碍潜在的诊断和治疗靶点。