Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.

Abstract

Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Krüppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to the <i>CORIN</i> promoter and enhances the promoter activity. Disruption of the <i>KLF17</i> gene in the endometrial cells abolishes <i>CORIN</i> expression. In mice, <i>Klf17</i> is up-regulated in the pregnant uterus. <i>Klf17</i> deficiency prevents uterine <i>Corin</i> expression in pregnancy. Moreover, <i>Klf17</i>-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulating <i>Corin</i> expression and uterine physiology in pregnancy.