Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy
Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy
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Krüppel 样因子 17 上调子宫 corin 表达并促进妊娠期螺旋动脉重塑
DOI：
10.1073/pnas.2003913117
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发表时间：
2020-07
影响因子：
11.1
通讯作者：
Qingyu Wu
中科院分区：
文献类型：
--
作者：
Can Wang;Zhiting Wang;Meiling He;Tiantian Zhou;Yayan Niu;Shengxuan Sun;Hui Li;Ce Zhang;Shengnan Zhang;Meng Liu;Ying Xu;Ningzheng Dong;Qingyu Wu
在怀孕期间，子宫内的血管增大，为生长中的胎儿提供更多的血液供应和营养。科林是一种促进这一过程的酶。在这项研究中，我们试图了解子宫蛋白的产生是如何控制的。在人类子宫细胞和怀孕小鼠的实验中，我们发现了一种叫做kr<s:1> ppel样因子17 （KLF17）的蛋白质，它可以打开怀孕子宫中的corin基因。在转基因小鼠中，Klf17缺乏会阻止子宫蛋白的产生，减小子宫血管大小，并导致妊娠期高血压。这些结果表明，KLF17是一种对妊娠期子宫功能有重要影响的基因控制蛋白。螺旋动脉重构是妊娠子宫内增加胎儿血流量的重要生理过程。螺旋动脉重塑受损会导致子痫前期，这是妊娠期的一种主要疾病。Corin是一种跨膜丝氨酸蛋白酶，在妊娠子宫中上调，促进螺旋动脉重构。迄今为止，子宫蛋白上调的机制尚不清楚。本研究表明kr<s:1> ppel样因子（KLF） 17是妊娠期子宫蛋白表达的关键转录因子。在体外培养的人子宫内膜细胞中，KLF17结合CORIN启动子并增强其活性。破坏子宫内膜细胞中的KLF17基因可消除CORIN的表达。在小鼠中，Klf17在妊娠子宫中上调。Klf17缺乏可抑制妊娠期子宫Corin的表达。此外，klf17缺陷小鼠的子宫螺旋动脉重塑不良，并发生妊娠高血压和蛋白尿。综上所述，我们的研究结果揭示了KLF17在妊娠期调节Corin表达和子宫生理方面的重要功能。
Significance In pregnancy, blood vessels in the uterus increase in size, providing more blood supply and nutrients to the growing fetus. Corin is an enzyme that boosts this process. In this study, we sought to understand how uterine corin production is controlled. In experiments with human uterine cells and pregnant mice, we identified a protein, called Krüppel-like factor 17 (KLF17), which turns on the corin gene in the pregnant uterus. In genetically modified mice, Klf17 deficiency prevents uterine corin production, decreases uterine vessel size, and causes high blood pressure in pregnancy. These results show that KLF17 is a gene-controlling protein important for uterus function in pregnancy. 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.
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影响因子：
4.8
作者：
Yan, W;Sheng, N;Wu, QY
通讯作者：
Wu, QY
影响因子：
3.7
作者：
Daftary GS;Zheng Y;Tabbaa ZM;Schoolmeester JK;Gada RP;Grzenda AL;Mathison AJ;Keeney GL;Lomberk GA;Urrutia R
通讯作者：
Urrutia R
DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Chaiworapongsa T;Chaemsaithong P;Yeo L;Romero R
通讯作者：
Romero R
影响因子：
9
作者：
Ali A;Zhang P;Liangfang Y;Wenshe S;Wang H;Lin X;Dai Y;Feng XH;Moses R;Wang D;Li X;Xiao J
通讯作者：
Xiao J
DOI：
--
发表时间：
2015
期刊：
--
影响因子：
--
作者：
Melissa E. Heard;Michael C. Velarde;L. Giudice;F. Simmen;M. RosaliaC.;Simmen
通讯作者：
Melissa E. Heard;Michael C. Velarde;L. Giudice;F. Simmen;M. RosaliaC.;Simmen