Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy
Top Cited Papers
- 21 March 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 484 (7393), 246-250
- https://doi.org/10.1038/nature10897
Abstract
Pregnant corin- or ANP-deficient mice have impaired trophoblast invasion and uterine spiral artery remodelling, and patients with pre-eclampsia have lower uterine corin messenger RNA and protein levels than normal pregnancies, suggesting that defects in corin and ANP function may contribute to pre-eclampsia. Corin is a cardiac protease that activates the cardiac hormone atrial natriuretic peptide (ANP), which lowers blood pressure. Corin expression has also been detected in the uterus. Qingyu Wu and colleagues now find that corin and ANP are involved in trophoblast invasion and spiral artery remodelling during pregnancy, and that loss of corin from the uterus causes pre-eclampsia-like symptoms in mice. The authors further show that pregnant women with pre-eclampsia have lower uterine levels of corin expression than women with normal pregnancies. They identify two mutations that reduce corin activity in pre-eclamptic patients. 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 unclear1,2. 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 pressure3. Unexpectedly, corin expression was detected in the pregnant uterus4. 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.Keywords
This publication has 35 references indexed in Scilit:
- Human Corin Isoforms with Different Cytoplasmic Tails That Alter Cell Surface TargetingPublished by Elsevier BV ,2011
- Ectodomain Shedding and Autocleavage of the Cardiac Membrane Protease CorinPublished by Elsevier BV ,2011
- Effects of anticoagulants on human plasma soluble corin levels measured by ELISAClinica Chimica Acta; International Journal of Clinical Chemistry, 2010
- Protease corin expression and activity in failing heartsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2010
- Plasma Soluble Corin in Patients With Heart FailureCirculation: Heart Failure, 2010
- The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in miceJCI Insight, 2009
- Corin: new insights into the natriuretic peptide systemKidney International, 2009
- Corin Variant Associated With Hypertension and Cardiac Hypertrophy Exhibits Impaired Zymogen Activation and Natriuretic Peptide Processing ActivityCirculation Research, 2008
- Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant miceNature Medicine, 2008
- Natriuretic peptides and hemodynamics in preeclampsiaAmerican Journal of Obstetrics and Gynecology, 2007