ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis.

ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis.
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DOI:
10.1016/j.bbrc.2021.02.144
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发表时间:
2021-04-23
影响因子:
3.1
通讯作者:
Jeong JW
Jeong JW
中科院分区:
生物学4区
文献类型:
--
作者:
Kim HI;Kim TH;Yoo JY;Young SL;Lessey BA;Ku BJ;Jeong JW

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子宫内膜异位症是一种疾病,通常局限于子宫内膜的子宫内膜细胞在宫腔外增殖,可导致盆腔疼痛和不孕。子宫内膜异位症患者在位内膜中ARID1A水平显著降低。子宫特异性ARID1A基因敲除的小鼠由于上皮孕酮受体(PGR)信号的丢失而不育。然而,ARID1A和PGR在子宫内膜异位症中的功能相关性尚未被研究。我们用免疫染色和Western印迹分析检测了ARID1A和PGR在患有和不患有子宫内膜异位症的在位内膜中的表达模式和共定位。在增殖期和分泌早期,ARID1A和PGR蛋白共定位于上皮细胞。我们的免疫沉淀分析和邻近连接分析(PLA)表明,在小鼠和人的子宫内膜上,ARID1A和PGR-A之间存在物理相互作用,而PGR-B没有相互作用。子宫内膜异位症患者在位内膜中ARID1A水平与PGR水平呈正相关。我们的研究结果为研究子宫内膜异位症中子宫内膜容受性和孕激素抵抗的分子机制提供了新的视角。ARID1A和PGR的相互关系可能有助于解释子宫内膜异位症相关性不孕症中非接受性子宫内膜的形成。
Endometriosis is a disorder in which endometrial cells normally limited to the lining of the uterus proliferate outside the uterine cavity and can cause pelvic pain and infertility. ARID1A levels are significantly reduced in the eutopic endometrium from women with endometriosis. Uterine specific Arid1a knock-out mice were infertile due to loss of epithelial progesterone receptor (PGR) signaling. However, the functional association of ARID1A and PGR in endometriosis has not been studied. We examined the expression patterns and co-localization of ARID1A and PGR in eutopic endometrium from women with and without endometriosis using immunostaining and Western blot analysis. ARID1A and PGR proteins co-localized in the epithelium during the proliferative and the early secretory phases. Our immunoprecipitation analysis and proximity ligation assay (PLA) revealed physical interaction between ARID1A and PGR-A but not PGR-B in the mouse and human endometrium. ARID1A levels positively correlated with PGR levels in the eutopic endometrium of women with endometriosis. Our results bring new perspectives on the molecular mechanisms involved in endometrial receptivity and progesterone resistance in endometriosis. The interrelationship between ARID1A and PGR may contribute to explaining the non-receptive endometrium in endometriosis-related infertility.
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