C-Peptide Inhibits Decidualization in Human Endometrial Stromal Cells via GSK3β-PP1

被引:9
|
作者
Khaliq, Sana Abdul [1 ,2 ,3 ]
Baek, Mi-Ock [1 ,2 ,3 ]
Cho, Hye-Jeong [2 ]
Chon, Seung Joo [4 ]
Yoon, Mee-Sup [1 ,2 ,3 ]
机构
[1] Gachon Univ, Sch Med, Dept Mol Med, Incheon, South Korea
[2] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Incheon, South Korea
[3] Gachon Univ, Dept Hlth Sci & Technol, GAIHST, Incheon, South Korea
[4] Gachon Univ, Gil Med Ctr, Coll Med, Dept Obstet & Gynecol, Incheon, South Korea
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2020年 / 8卷
基金
新加坡国家研究基金会;
关键词
C-peptide; GSK3 β PP1; decidualization; senescence; apoptosis; PREGNANCY LOSS; PROLIFERATION; SENESCENCE; EXPRESSION; APOPTOSIS; WOMEN;
D O I
10.3389/fcell.2020.609551
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Decidualization refers to the functional differentiation of endometrial stromal cells and plays a significant role in embryo implantation and pregnancy. C-peptide is excreted in equimolar concentrations as that of insulin during the metabolism of proinsulin in pancreatic beta-cells. High levels of C-peptide are correlated with hyperinsulinemia and polycystic ovarian syndrome, which show a defect in decidualization. However, the role of C-peptide in decidualization has not yet been studied. Here, we identified C-peptide as an endogenous antideciduogenic factor. This inhibitory function was confirmed by the reduced expression of decidual markers, including prolactin, insulin-like growth factor-binding protein-1, and Forkhead box protein O1 as well as by the fibroblastic morphological change in the presence of C-peptide. C-peptide also enhanced cellular senescence and decreased the proportion of apoptotic cells during decidualization. In addition, C-peptide potentiated the inhibitory effects of both insulin and palmitic acid in an AKT- and autophagy-independent manner, respectively. Furthermore, C-peptide augmented protein phosphatase 1 (PP1) activity, leading to a reduction in the inhibitory phosphorylation of glycogen synthase kinase (GSK)3 beta, which resulted in enhanced cellular senescence and decreased apoptosis during decidualization. Taken together, our findings suggest that C-peptide is an antideciduogenic factor acting via the regulation between PP1 and GSK3 beta in patients with hyperinsulinemia.
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收藏
页数:14
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