Abstract：
Gestational diabetes mellitus (GDM) is a common disorder in the clinic, which may lead to severe detrimental outcomes both for mothers and infants. However, the underlying mechanisms for GDM are still not clear. In the present study, we performed label-free proteomics using placentas from GDM patients and normal controls. Vitronectin caused our attention among differentially expressed proteins due to its potential role in the pathological progression of GDM. Vitronectin was increased in the placentas of GDM patients, which was confirmed by Western blot analysis. Vitronectin represses insulin signal transduction in trophoblast cells, whereas the knockdown of vitronectin further potentiates insulin-evoked events. Neutralization of CD51/61 abolishes the repressed insulin signal transduction in vitronectin-treated trophoblast cells. Moreover, vitronectin activates JNK in a CD51/61-depedent manner. Inhibition of JNK rescues impaired insulin signal transduction induced by vitronectin. Overall, our data indicate that vitronectin binds CD51/61 in trophoblast cells to activate JNK, and thus induces insulin resistance. In this regard, increased expression of vitronectin is likely a risk factor for the pathological progression of GDM. Moreover, blockade of vitronectin production or its receptors (CD51/61) may have therapeutic potential for dealing with GDM.
摘要：
妊娠期糖尿病(GDM)是临床常见疾病,这可能会对母亲和婴儿造成严重的不利后果。然而,GDM的潜在机制仍不清楚。在本研究中,我们使用GDM患者和正常对照胎盘进行了无标记蛋白质组学.由于玻连蛋白在GDM病理进展中的潜在作用，在差异表达蛋白中引起了我们的关注。Vitronectin在GDM患者的胎盘中升高，通过蛋白质印迹分析证实。玻连蛋白抑制滋养细胞中的胰岛素信号转导，而玻连蛋白的敲减进一步增强了胰岛素诱发的事件。CD51/61的中和消除了玻连蛋白处理的滋养层细胞中抑制的胰岛素信号转导。此外，玻连蛋白以CD51/61抑制的方式激活JNK。抑制JNK可挽救玻连蛋白诱导的胰岛素信号转导受损。总的来说,我们的数据表明玻连蛋白结合滋养细胞中的CD51/61激活JNK，从而诱导胰岛素抵抗。在这方面,玻连蛋白表达增加可能是GDM病理性进展的危险因素.此外，阻断玻连蛋白的产生或其受体（CD51/61）可能具有治疗GDM的潜力。
