Gestational diabetes mellitus (GDM) is a metabolic disorder whose major pathophysiological basis is demonstrated as placental insulin resistance (IR), while Smad4 always functions in the signal transduction of transforming growth factor beta (TGF‐β) pathway. Our study aims to figure out the role of Smad4 in an insulin resistance (IR) cellular model using placental trophoblast cell line. Importantly, HTR8‐Svneo cells, in the status of IR, indicated a significant increase in the expression of Smad4. Subsequently, the HTR8‐Svneo cell line with up‐regulated or depleted Smad4 was respectively achieved by the effective over‐expressed plasmid or siRNA of Smad4. We found out that the deficiency of Smad4 could promote the insulin sensitivity and restrict the inflammatory response in IR group of cells with significant augment in glucose uptake, up‐regulation of insulin signalling‐related molecules and attenuation in inflammatory biomarker expressions. On the contrary, the over‐expression of Smad4 showed a reversal effect on these alterations in IR group of cells. Besides, the positive effect of Smad4 on cell viability was also observed in our study.

中文翻译：

---

Smad4在HTR8-Svneo细胞中调节胰岛素抵抗，炎症和细胞增殖中的作用

妊娠期糖尿病（GDM）是一种代谢性疾病，其主要病理生理基础表现为胎盘胰岛素抵抗（IR），而Smad4始终在转化生长因子β（TGF-β）途径的信号转导中起作用。我们的研究旨在利用胎盘滋养层细胞系找出Smad4在胰岛素抵抗（IR）细胞模型中的作用。重要的是，处于IR状态的HTR8-Svneo细胞表明Smad4的表达显着增加。随后，分别通过有效过量表达的Smad4质粒或siRNA实现了Smad4上调或缺失的HTR8-Svneo细胞系。我们发现Smad4的缺乏可能会促进胰岛素敏感性并限制IR组细胞的炎症反应，并显着增加葡萄糖的摄取，胰岛素信号相关分子的上调和炎症生物标志物表达的减弱。相反，Smad4的过表达显示出对IR组细胞中这些变化的逆转作用。此外，在我们的研究中还观察到Smad4对细胞活力的积极作用。