SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.
SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.
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SOX6 和 PDCD4 通过 LPS 诱导的 miR-499 抑制增强心肌细胞凋亡
DOI：
10.1007/s10495-015-1201-6
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Jia Z;Wang J;Shi Q;Liu S;Wang W;Tian Y;Lu Q;Chen P;Ma K;Zhou C
脓毒症诱导的心肌细胞凋亡是导致心肌功能障碍的主要原因之一。由于它增强了许多促炎因子，脂多糖（LPS）被认为是该病理过程中的主要介质。然而，所涉及的详细机制尚不清楚。本研究旨在探讨脂多糖诱导心肌细胞凋亡的机制。我们发现LPS刺激抑制了microRNA（miR）-499的表达，从而上调了新生大鼠心肌细胞中SOX 6和PDCD 4的表达。我们证明SOX 6和PDCD 4是miR-499的靶基因，它们通过激活BCL-2家族途径增强LPS诱导的心肌细胞凋亡。通过过表达SOX 6或PDCD 4增强的凋亡过程被心脏丰富的miR-499拯救。过表达miR-499可保护心肌细胞免受LPS诱导的凋亡。简而言之，我们的研究结果证明了心肌细胞中存在miR-499-SOX 6/PDCD 4-BCL-2家族通路以响应LPS刺激。
Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.