C-Peptide Inhibits Decidualization in Human Endometrial Stromal Cells via GSK3β-PP1
- Authors
- Khaliq, S.A.; Baek, M.-O.; Cho, H.-J.; Chon, S.J.; Yoon, M.-S.
- Issue Date
- Nov-2020
- Publisher
- FRONTIERS MEDIA SA
- Keywords
- apoptosis; C-peptide; decidualization; GSK3 β; PP1; senescence
- Citation
- FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v.8
- Journal Title
- FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
- Volume
- 8
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79466
- DOI
- 10.3389/fcell.2020.609551
- ISSN
- 2296-634X
- Abstract
- 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)3β, 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 GSK3β in patients with hyperinsulinemia. © Copyright © 2020 Khaliq, Baek, Cho, Chon and Yoon.
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