Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy

Article

关键词: PROATRIAL NATRIURETIC PEPTIDE;    PLASMA SOLUBLE CORIN;    SERINE-PROTEASE;    PATHOGENESIS;    PREECLAMPSIA;    IMPLANTATION;    HYPERTENSION;   

DOI  :  10.1038/nature10897

来源: SCIE

【 摘 要 】

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(1,2). 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 pressure(3). Unexpectedly, corin expression was detected in the pregnant uterus(4). 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 inpre-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.

【 授权许可】

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