JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.12 P.990-998

http://doi.org/10.1631/jzus.B2000432

Silencing of DsbA-L gene impairs the PPARγ agonist function of improving insulin resistance in a high-glucose cell model

Author(s): Xuan Zhou, Jia-qi Li, Li-jie Wei, Meng-zhou He, Jing Jia, Jing-yi Zhang, Shao-shuai Wang, Ling Feng
Affiliation(s): Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Corresponding email(s): fltj007@163.com, colombo2008@sina.com
Key Words: Disulfide-bond A oxidoreductase-like protein (DsbA-L), Peroxisome proliferator-activated receptor γ, (PPARγ, ), Chemerin, Insulin signaling pathway, Gestational diabetes mellitus

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Abstract: )%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ; (PPARγ;) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.

高糖细胞模型中DsbA-L基因沉默损害PPARγ激动剂改善胰岛素抵抗的功能

目的:在高糖滋养细胞模型中,探讨二硫键A氧化还原酶样蛋白(DsbA-L)在过氧化物酶体增殖物激活受体γ(PPARγ)激动剂改善胰岛素抵抗过程中的作用,以及DsbA-L与趋化素(chemerin)的关系.
创新点:发现DsbA-L在PPARγ激动剂改善胰岛素抵抗的过程中起作用,并首次证明chemerin能促进DsbA-L的表达水平.
方法:采用免疫组织化学(IHC)和蛋白免疫印迹法(western blot)检测妊娠期糖尿病(GDM)患者与正常对照组孕妇的皮下脂肪组织中DsbA-L的定位和表达差异.在高糖滋养细胞模型中,通过western blot研究PPARγ激动剂和chemerin对DsbA-L蛋白的调节作用,并探究DsbA-L基因沉默对PPARγ激动剂调控胰岛素信号通路分子磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(PKB/AKT)和细胞外信号调节激酶1/2(ERK1/2)蛋白表达的影响.
结论:GDM患者的皮下脂肪组织中DsbA-L的水平较对照组低.PPARγ激动剂和chemerin均可增强DsbA-L蛋白的表达.DsbA-L基因沉默影响PPARγ激动剂对胰岛素信号PI3K-AKT通路的上调作用.
关键词：二硫键A氧化还原酶样蛋白(DsbA-L);过氧化物酶体增殖物激活受体γ(PPARγ);趋化素(Chemerin);胰岛素信号通路;妊娠期糖尿病

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高糖细胞模型中DsbA-L基因沉默损害PPARγ激动剂改善胰岛素抵抗的功能

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