An alternative splicing variant of mineralocorticoid receptor discovered in preeclampsia tissues and its effect on endothelial dysfunction  

作　　者：Mengxi Guo Chengliang Zhou Gufeng Xu Lin Tang Yechun Ruan Ying Yu Xianhua Lin Dandan Wu Hao Chen Priscilla Yu Luyang Jin Yinyu Wang Yimei Wu Kamran Ullah Tanzil Ur Rahman Xinmei Liu Jianzhong Sheng Hsiao-Chang Chan Hefeng Huang 

机构地区：[1]Women’s Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [2]International Peace Maternal and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China [3]Epithelial Cell Biology Research Center,Faculty of Medicine,School of Biomedical Sciences,The Chinese University of Hong Kong,Hong Kong,China [4]Key Laboratory of Reproductive Genetics,Ministry of Education(Zhejiang University),Hangzhou 310058,China [5]Department of Pathology and Pathophysiology,Zhejiang University School of Medicine,Hangzhou 310058,China [6]Shanghai Key Laboratory of Embryo Original Disease,Shanghai 20030,China

出　　处：《Science China(Life Sciences)》2020年第3期388-400,共13页中国科学（生命科学英文版）

基　　金：This work was supported by the National Key Research and Development Program of China(2017YFC1001303);International Cooperation Project of China and Canada NSFC(81661128010);National Natural Science Foundation of China(31471405,81671456,and 81671412);the National Key Basic Research Program(2013CB967404).

摘　　要：The pathophysiology of preeclampsia(PE)remains unclear.PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern.We collected placental and umbilical artery samples from normotensive and PE pregnancies.Mineralocorticoid receptor(MR)and its alternative splicing variant(ASV)expression and their biological effects on PE were examined.An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples(umbilical artery,~57.58%;placenta,~36.84%).The MR ASV expression was positively associated with blood pressure in both groups.The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways.The MR ASV can also impair the proliferation,migration,and tube formation ability of endothelial cells.These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology,especially in endothelial dysfunction,and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.The pathophysiology of preeclampsia (PE) remains unclear.PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern.We collected placental and umbilical artery samples from normotensive and PE pregnancies.Mineralocorticoid receptor (MR) and its alternative splicing variant (ASV) expression and their biological effects on PE were examined.An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples (umbilical artery,～57.58%;placenta,～36.84%).The MR ASV expression was positively associated with blood pressure in both groups.The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways.The MR ASV can also impair the proliferation,migration,and tube formation ability of endothelial cells.These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology,especially in endothelial dysfunction,and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.

关 键 词：PREECLAMPSIA MINERALOCORTICOID receptor ALTERNATIVE SPLICING variant OFFSPRING ENDOTHELIAL dysfunction 

分 类 号：R714.244[医药卫生—妇产科学]