Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Intensive care unit, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Cell Mol Med. 2024 Jul;28(14):e18546. doi: 10.1111/jcmm.18546.
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.
心力衰竭（HF）的预后取决于各种调节因素；微 RNA-128（miR-128）被鉴定为心脏纤维化的调节剂，导致 HF。肌细胞生成素家族抑制剂（MDFI），据报道与 Wnt/β-catenin 途径有关，据推测受 miR-128 调节。本研究探讨了 miR-128 在心肌细胞发育中的作用及其与 MDFI 的相互作用，并阐明了其在心脏损伤中的作用。基因表达谱通过 qPCR 和 Western blot 分析评估了 miR-128 对 HF 中 MDFI 表达的影响。荧光素酶测定研究了 miR-128 与 MDFI 之间的直接相互作用。MTT、transwell 和免疫组织化学评估了 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 与 MDFI 序列之间的相互作用。miR-128 模拟物显著降低 MDFI 的表达水平，mRNA 和蛋白水平分别降低 55%。miR-128 的过表达促进了凋亡，增加了 65%，并减弱了心肌细胞的增殖，而 MDFI 的上调显著增强了增殖。升高的 miR-128 水平上调了 Wnt1 和β-catenin 的表达，而升高的 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 的吸收降低了 MDFI 的表达，阻碍了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 可能促进心肌细胞增殖，突出了 miR-128/MDFI 相互作用在 HF 治疗中的潜在价值。
