Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.
Can WangZhiting WangMeiling HeTiantian ZhouYayan NiuShengxuan SunHui LiCe ZhangShengnan ZhangMeng LiuYing XuNingzheng DongQingyu WuPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
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 CORIN promoter and enhances the promoter activity. Disruption of the KLF17 gene in the endometrial cells abolishes CORIN expression. In mice, Klf17 is up-regulated in the pregnant uterus. Klf17 deficiency prevents uterine Corin expression in pregnancy. Moreover, Klf17-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 Corin expression and uterine physiology in pregnancy.
Keyphrases
- transcription factor
- poor prognosis
- pregnancy outcomes
- pregnant women
- preterm birth
- blood flow
- induced apoptosis
- binding protein
- gene expression
- dna binding
- blood pressure
- dna methylation
- endothelial cells
- genome wide identification
- long non coding rna
- cell cycle arrest
- genome wide
- endoplasmic reticulum stress
- cell proliferation
- adipose tissue
- smoking cessation
- high fat diet induced