Ma Xiao-Ling, Li Xiao-Cui, Tian Fu-Ju, Zhang Si-Ming, Liu Xiao-Rui, Zhang Yan, Fan Jian-Xia, Lin Yi
Institute of Embryo-Fetal Original Adult Disease, The International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
PLoS One. 2017 Jun 28;12(6):e0179852. doi: 10.1371/journal.pone.0179852. eCollection 2017.
To reveal the effect of p53-tristetraprolin-stathmin-1 signaling on trophoblasts and recurrent spontaneous abortion (RSA).
Stathmin-1 (STMN1), p53, and tristetraprolin (TTP) expression in paraffin-embedded villus tissue was determined using immunohistochemistry. HTR-8/SVneo cells were treated with doxorubicin to activate p53; STMN1 and TTP levels were detected by quantitative reverse transcription-PCR and western blotting. Western blotting and immunofluorescence were used to investigate STMN1 expression after TTP overexpression or knockdown in HTR-8 cells.
STMN1 was downregulated and p53 was upregulated in the villus tissue from patients with RSA. Doxorubicin decreased STMN1 expression but enhanced TTP expression in HTR-8 cells. In vitro, TTP overexpression inhibited STMN1 production; TTP knockdown promoted it. TTP downregulated STMN1 expression in trophoblasts by directly binding its 3' untranslated region.
TTP modulates trophoblast function and interacts with STMN1 and p53, and is related to pregnancy outcomes.
揭示p53-锌指蛋白-1-微管相关蛋白-1信号通路对滋养层细胞及复发性自然流产(RSA)的影响。
采用免疫组织化学法检测石蜡包埋绒毛组织中微管相关蛋白-1(STMN1)、p53和锌指蛋白(TTP)的表达。用阿霉素处理HTR-8/SVneo细胞以激活p53;通过定量逆转录聚合酶链反应和蛋白质免疫印迹法检测STMN1和TTP水平。在HTR-8细胞中过表达或敲低TTP后,采用蛋白质免疫印迹法和免疫荧光法研究STMN1的表达情况。
RSA患者绒毛组织中STMN1表达下调,p53表达上调。阿霉素降低了HTR-8细胞中STMN1的表达,但增强了TTP的表达。在体外,过表达TTP抑制了STMN1的产生;敲低TTP则促进了其产生。TTP通过直接结合滋养层细胞中STMN1的3'非翻译区下调其表达。
TTP调节滋养层细胞功能,并与STMN1和p53相互作用,与妊娠结局相关。