PDF(Pubmed)
Abstract：
Heart failure (HF) prognosis depends on various regulatory factors; microRNA-128 (miR-128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/β-catenin pathway, is supposed to be regulated by miR-128. This study investigates the interaction between miR-128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR-128\'s effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR-128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR-128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR-128 and MDFI sequences. miR-128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR-128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR-128 levels upregulated Wnt1 and β-catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR-128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR-128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/β-catenin pathway. Suppression of miR-128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR-128/MDFI interplay in HF treatment.
摘要：
心力衰竭（HF）的预后取决于各种调节因素；microRNA-128（miR-128）被鉴定为心脏纤维化的调节因子。有助于HF。MyoD家族抑制剂（MDFI），据报道，这与Wnt/β-catenin通路有关，应该由miR-128调节。本研究探讨了miR-128与MDFI在心肌细胞发育中的相互作用，并阐明了其在心脏损伤中的作用。基因表达谱分析使用qPCR和Western印迹分析评估miR-128对HF中MDFI表达的影响。荧光素酶测定研究了miR-128和MDFI之间的直接相互作用。MTT,transwell,和免疫组织化学评估miR-128和MDFI对HF小鼠心肌细胞的影响。基因扫描和荧光素酶测定验证了miR-128和MDFI序列之间的相互作用。miR-128模拟物显著降低mRNA和蛋白水平的MDFI表达,降低率为55%。miR-128过表达促进细胞凋亡，增加65%，抑制心肌细胞增殖，而MDFI上调显著增强增殖。miR-128水平上调Wnt1和β-连环蛋白表达，而增加的MDFI水平抑制了这些表达。苏木精和伊红染色的组织学分析显示，miR-128吸收降低了MDFI表达，阻碍细胞增殖和心脏修复，超声心动图显示心脏功能相应改善。我们的研究结果表明miR-128与MDFI相互作用，通过调节Wnt1/β-catenin通路在HF管理中发挥关键作用。抑制miR-128可促进心肌细胞增殖,强调miR-128/MDFI相互作用在HF治疗中的潜在价值。
