心房利钠肽（Atrial natriuretic peptide, ANP）是一种重要的生理激素，在调节机体水钠平衡和心血管稳态中起关键作用。Corin是一种从心脏中发现的跨膜丝氨酸蛋白酶，其功能为活化ANP。Corin缺陷可导致高血压、心脏病及子痫前期等重大疾病。多年来，人们一直认为心源性的ANP作为内分泌激素，经血循环到达肾脏，促进排钠利尿，调节体液平衡。我们最新发现，Corin、ANP及其受体在人各级肾小管的表达分布极其相似，提示肾脏可能也是ANP生成器官，在肾脏局部，Corin裂解生成ANP，ANP又以自分泌的方式原位作用于其受体，调节水钠平衡。本项目中，我们将用细胞生物学、生物化学及组织特异性条件敲除小鼠等方法，研究Corin表达于肾脏的生理意义，阐明心脏与肾脏的Corin-ANP通路在调控心功能、水钠平衡及血管稳态中的特殊作用，了解不同组织Corin-ANP失调引发疾病的机制。

Atrial natriuretic peptide (ANP) is an important hormone that regulates salt-water balance and cardiovascular homeostasis. Corin is a transmembrane serine protease discovered in the heart. The biological function of corin is to convert inactive pro-ANP to active ANP. Corin defects may lead to major cardiovascular diseases such as hypertension, heart disease and preeclampsia. For decades, ANP-mediated natriuretic response has been known as a cardiac endocrine function, in which heart-derived ANP circulates in the blood to reach the kidney where it promotes salt and water excretion, thereby regulating blood volume and pressure. Our latest results indicate that corin, ANP and the natriuretic peptide receptor-A are expressed similarly in human renal segments. The data suggest that corin-mediated ANP production may occur in the kidney and that locally produced ANP may act in an autocrine manner to regulate sodium and water reabsorption in situ. In this study, we plan to take cell biology, biochemistry and conditional knockout mouse model approaches to determine the physiological significance of renal corin expression. Our studies should help to elucidate the role of cardiac vs. renal corin-ANP pathway in regulating cardiac function, salt-water balance and vascular homeostasis. Our results may also help to understand how defects of the corin-ANP pathway in different organs contribute to cardiovascular and kidney diseases.