Document Detail


Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy.
MedLine Citation:
PMID:  22437503     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Yujie Cui; Wei Wang; Ningzheng Dong; Jinglei Lou; Dinesh Kumar Srinivasan; Weiwei Cheng; Xiaoyi Huang; Meng Liu; Chaodong Fang; Jianhao Peng; Shenghan Chen; Shannon Wu; Zhenzhen Liu; Liang Dong; Yiqing Zhou; Qingyu Wu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-21
Journal Detail:
Title:  Nature     Volume:  484     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-13     Completed Date:  2012-06-08     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  246-50     Citation Subset:  IM    
Affiliation:
Molecular Cardiology, Nephrology and Hypertension, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Atrial Natriuretic Factor / deficiency,  genetics,  metabolism
Blood Pressure / genetics
Case-Control Studies
Cells, Cultured
Disease Models, Animal
Female
Gene Expression Regulation
HEK293 Cells
Humans
Ischemia / metabolism,  pathology
Kidney / blood supply,  pathology
Kidney Diseases / genetics,  pathology
Mice
Mice, Knockout
Mice, Transgenic
Mutation
Pre-Eclampsia / genetics,  metabolism,  pathology,  physiopathology
Pregnancy
Serine Endopeptidases / chemistry,  genetics,  metabolism*
Trophoblasts / cytology*,  metabolism
Uterine Artery / growth & development*
Uterus / blood supply*,  metabolism*
Grant Support
ID/Acronym/Agency:
HD064634/HD/NICHD NIH HHS; HL089298/HL/NHLBI NIH HHS; R01 HD064634/HD/NICHD NIH HHS; R01 HL089298/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
85637-73-6/Atrial Natriuretic Factor; EC 3.4.21.-/CORIN protein, human; EC 3.4.21.-/Corin protein, mouse; EC 3.4.21.-/Serine Endopeptidases
Comments/Corrections

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