Study On The Regulatory Mechanism Of Shp2 Protein In Decidualization Of Human Uterine Stromal Cells

Decidualization refers to the uterine stromal cells converted to secreted decidual cells under the interaction of estrogen and progesterone and other factors.The process of decidualization is necessary for pregnancy and is used for subsequent embryo implantation and blastoderm development is an essential process for providing nutrients and immune substances.At present,it has been found that decidualization is accompanied by many signals like STAT3、AKT、and NF-κB,but the more detailed mechanism of decidualization has not yet been determined.Shp2 is a member of the protein tyrosine phosphatase family,which is involved in regulating life events such as cell proliferation、differentiation、movement、and apoptosis,and can mediate multiple signal transduction pathways such as MPKA and PI3K-AKT.We have confirmed that knock-out of Shp2 in the uterus of PR-cre mice can lead to early implantation failure;then we used knock-out of Shp2 in uterine stromal cells of Amhr2-cre mice and found that the mouse’s ability to give birth was weakened and embryos implantation were delayed;the uterine receptivity of the mouse is abnormal and decidualization is impaired.It was found that Shp2 may mediate the proliferation of mouse stromal cells through ERK signaling.On this basis,this experiment uses human uterine stromal cells(hESCs)to explore the functions and functions of Shp2 in hESCs decidualization using techniques such as protein immunoprecipitation,real-time quantitative PCR,cellular immunofluorescence,and RNA-sequence transcriptome analysis.The mechanism of action attempts to reveal the unique role of Shp2 in the decidual process of mouse and human endometrial stromal cells.The experiments in this subject found the following conclusions:(1)The expression of Shp2 in hESCs increased with the induction time,and knockdown of Shp2 prevented the expression of decidualizing marker IGFBP1、PRL and hindered the expression of decidualizing functional genes such as Wnt4、IL-11Rα、and VEGFA;Shp2 overexpression promoted the expression of decidualizing marker and decidualizing functional genes,indicating that Shp2 plays an important role in the decidualizing process of hESCs.(2)During in vitro hormone-induced decidualization,the induction of cAMP and progestin alone or in combination increased the expression of Shp2,while the induction of single estrogen or combination of cAMP and progesterone did not affect the expression of Shp2;experiments also found Shp2 is expressed in the nucleus and cytoplasm during induction,and Shp2 is mainly expressed in the nucleus as the induction time increases,which indicates that Shp2 is a diverse and dynamically regulated process in decidualization of hESCs.(3)RNA-Sequence transcriptome analysis found that Shp2 knockout could affect the decidualization cell cycle process and the regulation of multiple signaling pathways.Through further experiments,we found that Shp2 can regulate the cell cycle of decidualization of stromal cells and participate in signal transduction regulation of STAT3,ERK,AKT-FOXO1,which fully verified that Shp2 plays multiple roles in the process of decidualization of hESCs.In summary,our research shows that Shp2 participates in multiple transduction pathways in hESCs to regulate the decidualization process of stromal cells,and the role of Shp2 is diverse and dynamic.