Molecular insights into the corin function at the uteroplacental interface

In pregnancy, cell-cell interactions and tissue remodeling are important physiological processes at the uteroplacental interface. To date, molecular mechanisms governing cell activities at the uteroplacental interface are not fully understood. Corin is a proteolytic enzyme responsible for activating atrial natriuretic peptide (ANP), a multifunctional hormone essential for cardiovascular and metabolic homeostasis. Upon progesterone stimulation, corin expression is induced in the uterus via a specific set of transcription factors. Uterine corin activates ANP to enhance decidualization and cell-cell interactions within the vasculature, leading to sequential vascular smooth muscle and endothelial cell death in spiral arteries. These events are crucial for uterine vascular remodeling and trophoblast invasion. Corin also functions in the decidua to regulate macrophage distribution and function in response to placental ischemia. In mice, Corin knockout impairs endometrial decidualization, vascular remodeling, and macrophage function at the uteroplacental interface, causing a preeclampsia (PE)-like phenotype. In humans, deleterious variants and impaired epigenetic modifications in the CORIN gene have been reported in women with PE, indicating that corin deficiency may be a contributing factor in the pathogenesis of PE. In this review, we describe the corin function at the uteroplacental interface and underlying molecular mechanisms. We also discuss potential implications of corin deficiency in pregnancy-associated diseases.