Increased galectin-9 in pre-eclampsia impedes spiral artery remolding

【作者】 李彦虹； 林懿空； 田野； 叶云贞； 李大金； 杜美蓉；

【机构】 复旦大学附属妇产科医院； 北京师范大学；

【摘要】 Macrophages（Mm） are involved in spiral artery remodeling（SAR） in normal pregnancy.However,the underlying mechanism of Mm involved in preeclampsia（PE） remains unknown.Here,we found that trophoblasts-derived galectin-9（gal-9）was significantly higher in both placenta and plasma of PE patients than that of the healthy group.RhGal-9 treatment enhanced the adhesion of decidual Mcp to EVT cells via activating FAK/Src pathway.Moreover,gal-9 binding with CD44,induced the expansion of CD 11 c^high Mφ and enhanced their activated phenotype.IL-1β and TNF-α produced by CD 11 c^highMcp after gal-9 stimulation remarkably increased the apoptosis of EVT cells,which is adverse to SAR.In addition,gal-9/CD44 interaction promoted the ubiquitination of PKR1 and induced autophagy via the AMPK-mTOR pathway.The degradation of ubiquitination PKR1 mediated by the autophagy manner,led to the decreased IL-8 produced by Mcp.Accordingly,the tube formation and SAR were impaired due to the less IL-8.Therefore,our results revealed a new mechanism by which Mcp mediated abnormal SAR,and gal-9/CD44 is suggested to be a potential therapeutic target for PE.更多还原

【Abstract】 Macrophages（Mm） are involved in spiral artery remodeling（SAR） in normal pregnancy.However,the underlying mechanism of Mm involved in preeclampsia（PE） remains unknown.Here,we found that trophoblasts-derived galectin-9（gal-9）was significantly higher in both placenta and plasma of PE patients than that of the healthy group.RhGal-9 treatment enhanced the adhesion of decidual Mcp to EVT cells via activating FAK/Src pathway.Moreover,gal-9 binding with CD44,induced the expansion of CD 11 c^high Mφ and enhanced their activated phenotype.IL-1β and TNF-α produced by CD 11 c^highMcp after gal-9 stimulation remarkably increased the apoptosis of EVT cells,which is adverse to SAR.In addition,gal-9/CD44 interaction promoted the ubiquitination of PKR1 and induced autophagy via the AMPK-mTOR pathway.The degradation of ubiquitination PKR1 mediated by the autophagy manner,led to the decreased IL-8 produced by Mcp.Accordingly,the tube formation and SAR were impaired due to the less IL-8.Therefore,our results revealed a new mechanism by which Mcp mediated abnormal SAR,and gal-9/CD44 is suggested to be a potential therapeutic target for PE.更多还原