1. Interleukin-13 receptor subunit alpha-2 is a target of progesterone receptor and steroid receptor coactivator-1 in the mouse uterus†
- Author
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Tae Hoon Kim, Brandon Lee, Jae Wook Jeong, Francesco J. DeMayo, Kevin Lee, and Ryan M. Marquardt
- Subjects
0301 basic medicine ,Stromal cell ,medicine.drug_class ,medicine.medical_treatment ,Biology ,Endometrium ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Nuclear Receptor Coactivator 1 ,Progesterone receptor ,medicine ,Animals ,RNA, Messenger ,RNA, Small Interfering ,Mice, Knockout ,Uterus ,IL13RA2 ,Decidualization ,Cell Biology ,General Medicine ,Cell biology ,Insulin-Like Growth Factor Binding Protein 1 ,Steroid hormone ,030104 developmental biology ,medicine.anatomical_structure ,Reproductive Medicine ,Gene Expression Regulation ,Estrogen ,030220 oncology & carcinogenesis ,Interleukin-13 Receptor alpha2 Subunit ,Female ,RNA Interference ,Hormone ,Research Article - Abstract
The endometrium, composed of epithelial and stromal cell compartments, is tightly regulated by the ovarian steroid hormones estrogen (E2) and progesterone (P4) during early pregnancy. Through the progesterone receptor (PGR), steroid receptor coactivators, and other transcriptional coregulators, progesterone inhibits E2-induced cell proliferation and induces the differentiation of stromal cells in a process called decidualization to promote endometrial receptivity. Although interleukin-13 receptor subunit alpha-2 (Il13ra2) is expressed in the human and mouse endometrium, its potential role in the steroid hormone regulation of the endometrium has not been thoroughly examined. In this study, we employed PGR knockout mice and steroid receptor coactivator-1 knockout mice (SRC-1−/−) to profile the expression of Il13ra2 in the murine endometrium and determine the role of these transcriptional regulators in the hormone-responsiveness of Il13ra2 expression. Furthermore, we utilized a well-established decidualization-inducing steroidogenic cocktail and a siRNA-based knockdown of IL13RA2 to determine the importance of IL13RA2 in the decidualization of primary human endometrial stromal cells. Our findings demonstrate that Il13ra2 is expressed in the subepithelial stroma of the murine endometrium in response to ovarian steroid hormones and during early pregnancy in a PGR- and SRC-1-dependent manner. Furthermore, we show that knockdown of IL13RA2 before in vitro decidualization of primary human endometrial stromal cells partially compromises the full decidualization response. We conclude that Il13ra2 is a downstream target of progesterone through PGR and SRC-1 and plays a role in mediating the stromal action of ovarian steroid hormones.
- Published
- 2020