Hussain Khadam, Khurram Somia, Yousaf Muhammad, Ishtiaq Ayesha, Mushtaq Iram, Ali Tahir, Murtaza Iram
Department of Biochemistry, Signal Transduction Laboratory, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China.
J Cardiovasc Transl Res. 2025 Jun 23. doi: 10.1007/s12265-025-10636-9.
Pathological growth of cardiomyocytes known as cardiac hypertrophy (CH). Differential expressions of miRNAs have an immense therapeutic potential against cardiac hypertrophy. The current study aim is to evaluate the therapeutic potential of miRNA-137-3p/383-5p in cardiac hypertrophy by regulation of PGC-1α signaling nexus. Silencing of pro-hypertrophic miRNAs e.g. miR-137-3p and miR-383-5p leads to the restoration of their common target gene PGC-1α in hypertrophic cells. Interestingly, the results of this invivo study showed the cardioprotective effects of these antagomirs. Moreover, PGC-1α associated signaling events e.g. fatty acid oxidation (Cpt1a, Cpt1b), mitochondria membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), oxidative phosphorylation (Ndufa6, Atp5me), apoptosis (Bcl-2, BAX), antioxidants (SOD, GSH, CAT), mitochondrial dynamic (Mfn-2, Drp-1) were significantly restored in the treated groups of miRNA antagomirs. Conclusively, this study uncovers that the pharmacological inhibition of miR-137-3p and miR-383-5p have a potential to rescue from the cardiac hypertrophy by regulation of PGC-1α signaling nexus.
被称为心肌肥大（CH）的心肌细胞病理性生长。微小RNA（miRNA）的差异表达在对抗心肌肥大方面具有巨大的治疗潜力。当前研究的目的是通过调节PGC-1α信号通路来评估miRNA-137-3p/383-5p在心肌肥大中的治疗潜力。促肥大性miRNA（如miR-137-3p和miR-383-5p）的沉默导致其共同靶基因PGC-1α在肥大细胞中得以恢复。有趣的是，这项体内研究的结果显示了这些拮抗剂的心脏保护作用。此外，在miRNA拮抗剂治疗组中，与PGC-1α相关的信号事件，如脂肪酸氧化（Cpt1a、Cpt1b）、线粒体膜电位（MMP）、线粒体活性氧（mtROS）、氧化磷酸化（Ndufa6、Atp5me）、细胞凋亡（Bcl-2、BAX）、抗氧化剂（SOD、GSH、CAT）、线粒体动力学（Mfn-2、Drp-1）均得到显著恢复。总之，本研究揭示了对miR-137-3p和miR-383-5p的药理学抑制有可能通过调节PGC-1α信号通路来挽救心肌肥大。
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