IGF2 Regulates The Expression Of Autophagy In Placenta Of Severe Preeclampsia And Its Significance

Preeclampsia(PE)is one of the most important hypertensive disorders of pregnancy.It usually occurs after 20 weeks of pregnancy.The main characteristic of the patients is hypertension and proteinuria.Severe cases can lead to cerebral edema and cerebral hemorrhage,Pulmonary edema,placental abruption,fetal growth restriction(FGR)and complications such as intrauterine fetal death are one of the causes of maternal and perinatal mortality.They may even directly cause 10%-15% of maternal deaths.At present,various theories can not completely elucidate its causes and pathogenesis,and many studies suggest that the incidence of preeclampsia can be divided into placenta malformation and placental oxidative stress.Recent studies found that placental autophagy may be closely related with the incidence of preeclampsia.A variety of cell-conduction signals are involved in the regulation of autophagy,of which PI3 K / Akt / mTOR(phosphatidylinositol 3-kinase / protein kinase B / rapamycin target)is more commonly recognized.Mammalian mammalian target of Rapamyc(mTOR)inhibits the formation and maturation of autophagic vacuoles.The BECN1(Beclin1)gene is a mammalian gene that is involved in autophagy and is a component of the PI3 K complex.LC3 is microtubule-associated protein 1 and light chain 3,LC3 exists in soluble LC3-I and membrane-bound LC3-II in two forms,in the process of autophagy LC3-I to LC3-II transformation,its content and autophagy The number of the body was positively correlated.These three are important autophagy-related proteins,LC3-II,Beclin1 is more as a marker of autophagy protein.IGF2 is a small molecule glycoprotein expressed primarily in the embryonic phase.It has the role of promoting cell mitosis,promoting differentiation,regulating metabolism and anti-apoptosis.Objective: This study was designed to investigate the expression and correlation of IGF2 protein and autophagy-related proteins mTOR,Beclin1,and LC3-II in placenta of severe preeclampsia(SE).Methods: Totally 30 patients with severe preeclampsia admitted to Shengjing Hospital of China Medical University from July 2015 to February 2017 were recruited and 30 pregnant women with normal blood pressure during the third trimester of pregnancy were selected as controls.The expression of IGF2 and autophagy-related proteins in 30 cases of preeclampsia and 30 cases of normal placenta were detected by Western Blot and immunohistochemistry.The expressions of IGF2 and autophagy-related proteins in severe placenta from preeclampsia The relationship between trophoblast ultrastructur e and autophagosome was observed by transmission electron microscope.Results: The results of immunohistochemistry showed that IGF2,Beclin1,LC3-II and mTOR were expressed in placenta of SE group and control group.The high expression rate of IGF2 in SE group was 30%,the high expression rate of IGF2 in control group was 56.67%,the high expression rate of IGF2 in SE group was significantly lower than that in control group(P <0.01);the high expression rate of mTOR in SE group was 20%,The high expression rate of mTOR in control group was 56.67%,the high expression rate of mTOR in SE group was significantly lower than that in control group(P <0.01);the high expression rate of Beclin1 in SE group was 76.67%,the high expression rate of Beclin1 in control group was The high expression rate of Beclin1 in SE group was significantly higher than that in control group(P <0.01).The high expression rate of LC3-II in SE group was 60% and the high expression rate of LC3-II in control group was 16.67% The high expression rate of LC3-II was significantly higher than that of the control group(P <0.01).Western Blot method for IGF2,mTOR,Beclin1 and LC3-II in the SE group and the control group expression content semi-quantitative.The results showed that the relative content of IGF2 in SE group was 0.48 ± 0.16,the relative content of IGF2 in control group was 1 ± 0.21,the expression of IGF2 in SE group was significantly lower than that in control group(P <0.05);the relative content of mTOR in SE group was 0.44 ± 0.08,The relative content of mTOR in control group was 1 ± 0.26,the expression of mTOR in SE group was significantly lower than that in control group(P <0.05);the relative content of Beclin1 in SE group was 3.45 ± 0.95,the relative content of Beclin1 in control group was 1 ± 0.23,The expression of Beclin1 in SE group was significantly higher than that in control group(P <0.05).The relative content of LC3-II in SE group was 3.50 ± 0.52,while the relative content of LC3-II in control group was 1 ± 0.17 Higher than the control group(P <0.05).Spearman correlation analysis was used to compare the positive expression rate of IGF2 and the expression of autophagy-related protein mTOR,Beclin1,LC3-II in SE group.Expressions of IGF2 and mTOR between the correlation coefficient was 0.440,P = 0.015;IGF2 and Beclin1 expression rate between the correlation coefficient-0.417,P = 0.022.The correlation coefficient between the expression rates of IGF2 and LC3-II was-0.539,P = 0.002,indicating that there was a correlation between IGF2 and autophagy-related protein expression intensity.The formation of autophagosomes with typical bilayer membrane structure in placental cytoplasm of severe preeclampsia and the formation of autophagic lysosomes with monolayers surrounding the intact organelles were observed under transmission electron microscope.Conslusions:IGF2-mediated autophagy may be related to the preeclampsia,and the expression of IGF2 in the placenta of preeclampsia is reduced.The role of autophagy is regulated by mTOR pathway,leading to over-autophagy and placental dysplasia.