オカダ　ヒデタカ   OKADA HIDETAKA   岡田　英孝    所属   関西医科大学  産科学・婦人科学講座    職種   教授
論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	The transcription factor HAND2 up-regulates transcription of the IL15 gene in human endometrial stromal cells
掲載誌名	正式名：The Journal of biological chemistry 略　 称：J Biol Chem ISSNコード：00219258/1083351X
掲載区分	国外
巻・号・頁	295(28),pp.9596-9605
著者・共著者	Murata H, Tanaka S, Tsuzuki-Nakao T, Kido T, Kakita-Kobayashi M, Kida N, Hisamatsu Y, Tsubokura H, Hashimoto Y, Kitada M, Okada H
担当区分	最終著者
発行年月	2020/07
概要	Cyclic changes of the human endometrium, such as proliferation, secretion, and decidualization, occur during regular menstrual cycles. Heart- and neural crest derivatives-expressed transcript 2 (HAND2) is a key transcription factor in progestin-induced decidualization of human endometrial stromal cells (ESCs). It has been suggested that HAND2 regulates interleukin 15 (IL15), a key immune factor required for the activation and survival of uterine natural killer (uNK) cells. Activated uNK cells can promote spiral artery remodeling and secrete cytokines to induce immunotolerance. To date, no studies have evaluated the transcription factors that regulate IL15 expression in human ESCs. In the present study, we examined whether HAND2 controls IL15 transcriptional regulation in human ESCs. Quantitative RT-PCR and histological analyses revealed that HAND2 and IL15 levels increase considerably in the secretory phase of human endometrium tissues. Results from ChIP-quantitative PCR suggested that HAND2 binds to a putative HAND2 motif, which we identified in the upstream region of the human IL15 gene through in silico analysis. Using a luciferase reporter assay, we found that the upstream region of the human IL15 gene up-regulates reporter gene activities in response to estradiol and a progestin representative (medroxyprogesterone) in ESCs. The upstream region of the human IL15 gene also exhibited increasing responsiveness to transfection with a HAND2 expression vector. Of note, deletion and substitution variants of the putative HAND2 motif in the upstream region of IL15 did not respond to HAND2 transfection. These findings confirm that HAND2 directly up-regulates human IL15 transcription in ESCs.
DOI	10.1074/jbc.RA120.012753
PMID	32444497