mTOR和PLGF在胎儿宫内生长受限中的作用机制

胎儿宫内生长受限(IUGR)是一种常见孕期疾病,有报道称其与滋养细胞的侵袭能力减弱有关,而mTOR和PLGF对滋养细胞侵袭有重要作用。为了探究m TOR和PLGF对滋养细胞侵袭力的影响,明确两者在IUGR发生和发展过程中的作用机制,本研究以孕早期人滋养细胞Swan 71为对象,利用雷帕霉素抑制mTOR的活化,通过小室侵袭实验、基因沉默和蛋白印迹法(Western blotting)观察了滋养细胞侵袭力和相关基因表达的变化,以及外源PLGF的添加对其结果有无影响。结果表明m TOR磷酸化受到抑制会导致滋养细胞的侵袭能力减弱,而PLGF能改善这种减弱现象,改善机制与增强p70、ERK和AKT磷酸化有关。然而,当mTOR基因被沉默后,PLGF就不能再改善或逆转因m TOR磷酸化缺失带来的细胞侵袭力的减弱。此外,本研究还发现mTOR磷酸化能调控PLGF和sflt-1的表达,后两者在IUGR发展中,常因为滋养细胞侵袭力的减弱而受到影响。

The Function of mTOR and PLGF on Intrauterine Growth Restriction

Intrauterine growth restriction(IUGR) is a common pregnancy disease,which has been reported to be associated with decreased invasiveness of trophoblast cells,while m TOR and PLGF play an important role in trophoblast invasion.In order to explore the effects of m TOR and PLGF on the invasiveness of trophoblasts,and to explain the mechanism of mTOR and PLGF in the development and progression of IUGR,we took first trimester human trophoblast Swan 71 cell as study object,inhibit the activation of mTOR by rapamycin,the chamber invasion assay,siRNA and Western blotting analysis were used to observe the changes of trophoblast invasion and related gene expression,and we also investigated the effect of exogenous PLGF on the previous results.The results indicated that inhibition of m TOR phosphorylation leads to a decrease in the invasive ability of trophoblasts,whereas PLGF could ameliorate this attenuating phenomenon,and the mechanism of improvement was associated with enhanced phosphorylation of p70,ERK and AKT.However,when the mTOR gene was silenced,PLGF could no longer change the decrease in cell invasiveness due to m TOR phosphorylation loss.In addition,this study also found that mTOR phosphorylation could regulate the expression of PLGF and sflt-1,in the development of IUGR,PLGF and sflt-1 were often affected by the weakening of trophoblast invasion.