title: Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy.
abstract: In pregnancy, trophoblast invasion and uterine spiral artery remodelling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodelling has been implicated in pre-eclampsia, a major complication of pregnancy, for a long time but the underlying mechanisms remain unclear. Corin (also known as atrial natriuretic peptide-converting enzyme) is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone that is important in regulating blood pressure. Unexpectedly, corin expression was detected in the pregnant uterus. Here we identify a new function of corin and ANP in promoting trophoblast invasion and spiral artery remodelling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of pre-eclampsia. In these mice, trophoblast invasion and uterine spiral artery remodelling were markedly impaired. Consistent with this, the ANP potently stimulated human trophoblasts in invading Matrigels. In patients with pre-eclampsia, uterine Corin messenger RNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified Corin gene mutations in pre-eclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to pre-eclampsia.
authors.affiliation: Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ningzheng
authors.initials: N
authors.lastname: Dong
authors.forename: Jinglei
authors.initials: J
authors.lastname: Lou
authors.forename: Dinesh Kumar
authors.initials: DK
authors.lastname: Srinivasan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cheng
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Huang
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Chaodong
authors.initials: C
authors.lastname: Fang
authors.forename: Jianhao
authors.initials: J
authors.lastname: Peng
authors.forename: Shenghan
authors.initials: S
authors.lastname: Chen
authors.forename: Shannon
authors.initials: S
authors.lastname: Wu
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Wu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D055988:Uterine Artery / Q000254:growth & development*; D014599:Uterus / Q000098:blood supply* / Q000378:metabolism*
chemical_list: D009320:Atrial Natriuretic Factor; C119812:CORIN protein, human; C485617:Corin protein, mouse; D012697:Serine Endopeptidases