| Objective: Some studies have pointed out that abnormal activation of Fyn will lead to excessive proliferation and invasion of cells.Abnormal invasion of trophoblasts is the pathogenesis of placental accreta,and the process of trophoblast invasion into myometrium of uterus is similar to the migration and infiltration of tumor cells.Therefore,the purpose of this study is to explore the expression changes of Fyn in placenta of patients with placental accreta and further explore the related mechanism.Methods:(1)The experimental group was selected from 4 pregnant women who were admitted to the obstetrics department of Affiliated Hospital of Jining Medical College from January 2020 to June 2020 for lower uterine cesarean section and were diagnosed with placenta implantation and 4 healthy pregnant women without pregnancy complications,all of whom were terminated by cesarean section,and the pregnant women were divided into the placenta implantation group and the control group.In the control group,the placenta was taken from healthy pregnant women without pregnancy complications,and the placenta in the implantation group was taken from the placental adhesion area and the deep infiltrated area of the myometrium,and a piece of placental tissue of about 1 cm×1 cm×0.5 cm was collected from each of them.One part of the separated placenta samples was paraffin-embedded;the other part was rapidly frozen at-80°C.(2)By high-throughput sequencing,Fyn was found to be the most significant difference between the placenta implantation group and the control group.(3)q PCR,Westernblot,and immunohistochemical assays were used to detect the expression of Fyn between the placenta implantation and control groups.(4)After knockdown of Fyn,the knockdown efficiency of Fyn was determined by q PCR,and the migration ability and invasion ability of human chorionic villous trophoblast(HTR8/SVneo)cells were detected by scratch assay and Transwell assay.(5)Westernblot was performed to detect the protein expression of STAT3,p38,JNK,p-STAT3,p-p38 and p-JNK in the knockdown group as well as in the control group.(6)After inhibiting STAT3,p38,and JNK in HTR8/SVneo cells with inhibitors,the migratory ability and invasive ability of HTR8/SVneo cells were detected using scratch assay and Transwell assay.Results:(1)Fyn was found to be the most significantly different gene between the placental implantation group and the control group using high-throughput sequencing.(2)The m RNA and protein expression levels of Fyn were found to be significantly higher than those of the control group by q PCR,Westernblot,and immunohistochemistry experiments.(3)Westernblot results showed significantly higher levels of p-STAT3,p-p38,and p-JNK in the placental implantation group.(4)We also found that after knockdown of Fyn,the results of Transwell assay and scratch assay showed that the migration and invasion ability of HTR8/SVneo cells were significantly reduced,and Westernblot revealed that the levels of pSTAT3,p-p38 and p-JNK were significantly inhibited because of the knockdown of Fyn.(5)We also found that the invasion and migration ability of HTR8/SVneo cells could be significantly reduced after inhibiting STAT3,p38 and JNK protein activities by employing inhibitors.Conclusion: Our study found that Fyn mediates excessive invasion and migration of placental trophoblasts through STAT3,p38 and JNK pathways.Clinical samples and in vitro experiments reveal the role of Fyn in the invasion and migration of placental trophoblasts.These results provide new insights into the unique role of Fyn in placental accreta,and provide reference for further research and insights on Fyn as a therapeutic target for placenta accreta in the future.These results provide new insights into the unique role of Fyn in placental accreta,and provide reference for further research and insights on Fyn as a therapeutic target for placenta accreta in the future. |
PDF Full Text Request