Inhibition of myocyte-specific enhancer factor 2A improved diabetic cardiac fibrosis partially by regulating endothelial-to-mesenchymal transition.
Inhibition of myocyte-specific enhancer factor 2A improved diabetic cardiac fibrosis partially by regulating endothelial-to-mesenchymal transition.
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抑制肌细胞特异性增强因子 2A 通过调节内皮间质转化部分改善糖尿病心脏纤维化
DOI：
10.18632/oncotarget.8842
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Zhang MX
中科院分区：
文献类型：
--
作者：
Chen XY;Lv RJ;Zhang W;Yan YG;Li P;Dong WQ;Liu X;Liang ES;Tian HL;Lu QH;Zhang MX
心脏纤维化是糖尿病心肌病的重要病理过程，其潜在机制仍不清楚。本研究试图确定抑制肌细胞增强因子 2A (MEF2A) 是否可以通过部分调节内皮间质转化 (EndMT) 来减轻心脏纤维化。我们使用毒素链脲佐菌素 (STZ) 诱导小鼠患 1 型糖尿病，并在心肌中注射慢病毒介导的短发夹 RNA (shRNA) 以抑制 MEF2A 表达。 STZ 注射后二十一周检查蛋白质表达、组织学和功能参数。我们发现糖尿病通过EndMT成纤维细胞的积累增加心脏MEF2A的表达，加重心功能障碍和心肌纤维化。所有这些特征都被 MEF2A 抑制所消除。在培养的人脐静脉内皮细胞 (HUVEC) 中通过 shRNA 沉默 MEF2A 基因，通过与 p38MAPK 和 Smad2 相互作用，改善高葡萄糖诱导的表型转变和间充质标记物的获得。我们的结论是，通过与 p38MAPK 和 Smad2 相互作用部分抑制 EndMT，抑制内皮细胞来源的 MEF2A 可能有助于预防糖尿病诱导的心脏纤维化。
Cardiac fibrosis is an important pathological process of diabetic cardiomyopathy, the underlying mechanism remains elusive. This study sought to identify whether inhibition of Myocyte enhancer factor 2A (MEF2A) alleviates cardiac fibrosis by partially regulating Endothelial-to-mesenchymal transition (EndMT). We induced type 1 diabetes mellitus using the toxin streptozotocin (STZ) in mice and injected with lentivirus-mediated short-hairpin RNA (shRNA) in myocardium to inhibit MEF2A expression. Protein expression, histological and functional parameters were examined twenty-one weeks post-STZ injection. We found that Diabetes mellitus increased cardiac MEF2A expression, aggravated cardiac dysfunction and myocardial fibrosis through the accumulation of fibroblasts via EndMT. All of these features were abolished by MEF2A inhibition. MEF2A gene silencing by shRNA in cultured human umbilical vein endothelial cells (HUVECs) ameliorated high glucose–induced phenotypic transition and acquisition of mesenchymal markers through interaction with p38MAPK and Smad2. We conclude that inhibition of endothelial cell-derived MEF2A might be beneficial in the prevention of diabetes mellitus-induced cardiac fibrosis by partially inhibiting EndMT through interaction with p38MAPK and Smad2.
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