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

• Published in: Frontiers in cell and developmental biology 2020-11, Vol.8, p.609551-609551
• Main Authors: Khaliq, Sana Abdul, Baek, Mi-Ock, Cho, Hye-Jeong, Chon, Seung Joo, Yoon, Mee-Sup
• Format: Article
• Language: English
• Subjects: apoptosis; C-peptide; Cell and Developmental Biology; decidualization; GSK3 β; PP1; senescence
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2020.609551

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.