논문 상세보기
Studies of Kruppel like factor4 and Kruppel like factor 15 in uterus
For successful embryo implantation, the stromal cells of the endometrium are morphologically and functionally differentiated into decidual cells. In the endometrium, estrogen induces proliferation of epithelial cells, but progesterone regulates the differentiation of epithelial cells, leading to decidualization of stromal cells. Kruppel like factor (KLF) is a zinc finger DNA binding protein that regulates transcription and has a wide range of functions in the cell cycle, cell apoptosis and differentiation control. In the uterus, KLF9, 13 plays an important role in implantation and decidual cell differentiation. KLF4 and KLF15 regulate the proliferation and differentiation of endometrial epithelial cells, but their role in stromal cells is unknown. In this study, we investigated the role of KLF4 and KLF15 in endometrial stromal cells. In mouse uterus, KLF4 was expressed in proliferative phase of glandular and luminal epithelial cells. However in endometrial stromal cells, KLF4 was highly expressed in secretory phase and secondary decidual zone after implantation. The expression of KLF15 was little in cytoplasm of luminal and glandular epithelial cells and proliferated in nucleus of secretory phase stromal cell.herefore, KLF4 and 15 are thought to be important for decidualization. To investigate the effect of estrogen and progesterone on the expression of KLF4 and KLF15, uterus of ovariectomy (OVX) mice which were injcected 17β- estradiol (E2, 0.3 mg) and progesterone (P4, 1 mg) and both ERα-knock out and wild type (diestrus, estrus) mice were used. KLF4 in OVX+E2 group was significantly higher than OVX+E2 / P4 group was lower than OVX+E2 group. There was no significant difference between ERαKO and WT diestrus group and significantly lower than WT estrus group. Expression of KLF15 was higher in the OVX+ P4 group than in the OVX group and lower in the OVX+E2 group. The OVX+E2 / P4 group was higher than the OVX+E2 group. There was no difference between ERαKO and WT diestrus. The differences in expression of KLF4 and KLF15 by P4 in OVX mouse uterine tissues may be due to the tissue specific expression pattern of epithelial (KLF4) and stromal cells (KLF15). The expression of KLF4 and KLF15 was increased by treatment of cyclic adenosine monophostphate (cAMP, 0.5 mM) and medroxyprogesterone acetate (MPA, 1μM) in human endometrial stromal cells. KLF15 siRNA increased the expression of decidualization markers (BMP2, IGFBP-1 and prolactin) with increasing progesterone receptor A/B (PR A/B), while KLF4 siRNA treatment decreased expression of decidualization markers. There was no significant difference in cell proliferation and apoptosis markers in KLF4 / 15 siRNA treatment. Therefore, progesterone induces KLF4 to promote decidualization, while normally induced KLF15 inhibits progesterone receptor expression. Expression of KLF4 in endometrial epithelium is induced by estrogen but induced by progesterone to promote decidualization, and KLF15 is mainly induced by progesterone in stromal cells and inhibit excessive PR A / B activity.
