Abstract：
SCN5A mutations have been reported to cause various cardiomyopathies in humans. Most of the SCN5A mutations causes loss of function and thereby, alters the overall cellular function. Therefore, to understand the loss of SCN5A function in cardiomyocytes, we have knocked down the SCN5A gene (SCN5A-KD) in H9c2 cells and explored the cell phenotype and molecular behaviors in the presence and absence of isoproterenol (ISO), an adrenergic receptor agonist that induces cardiac hypertrophy. Expression of several genes related to hypertrophy, inflammation, fibrosis, and energy metabolism pathways were evaluated. It was found that the mRNA expression of hypertrophy-related gene, brain (B-type) natriuretic peptide (BNP) was significantly increased in SCN5A-KD cells as compared to \'control\' H9c2 cells. There was a further increase in the mRNA expressions of BNP and βMHC in SCN5A-KD cells after ISO treatment compared to their respective controls. Pro-inflammatory cytokine, tumor necrosis factor-alpha expression was significantly increased in \'SCN5A-KD\' H9c2 cells. Further, metabolism-related genes like glucose transporter type 4, cluster of differentiation 36, peroxisome proliferator-activated receptor alpha, and peroxisome proliferator-activated receptor-gamma were significantly elevated in the SCN5A-KD cells as compared to the control cells. Upregulation of these metabolic genes is associated with increased ATP production. The study revealed that SCN5A knock-down causes alteration of gene expression related to cardiac hypertrophy, inflammation, and energy metabolism pathways, which may promote cardiac remodelling and cardiomyopathy.
摘要：
已经报道SCN5A突变在人类中引起各种心肌病。大多数SCN5A突变会导致功能丧失，改变整体细胞功能。因此,为了了解心肌细胞中SCN5A功能的丧失，我们在H9c2细胞中敲除了SCN5A基因(SCN5A-KD)，并探索了在存在和不存在异丙肾上腺素(ISO)的情况下的细胞表型和分子行为，一种诱导心脏肥大的肾上腺素能受体激动剂。肥大相关基因的表达,炎症,纤维化，和能量代谢途径进行了评估。发现肥大相关基因的mRNA表达,与“对照”H9c2细胞相比，SCN5A-KD细胞中的脑（B型）利钠肽（BNP）显着增加。与各自的对照相比,ISO处理后SCN5A-KD细胞中BNP和βMHC的mRNA表达进一步增加。促炎细胞因子，肿瘤坏死因子α在SCN5A-KDH9c2细胞中的表达显著增加。Further,代谢相关基因，如葡萄糖转运蛋白4型，分化簇36，过氧化物酶体增殖物激活受体α，与对照细胞相比，SCN5A-KD细胞中过氧化物酶体增殖物激活受体-γ显著升高。这些代谢基因的上调与ATP产生增加有关。研究表明，SCN5A敲低导致与心脏肥大相关的基因表达改变，炎症,和能量代谢途径，这可能会促进心脏重塑和心肌病。
