{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:42:49Z","timestamp":1787884969473,"version":"build-2784847793"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2704500"],"award-info":[{"award-number":["2022YFC2704500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702400"],"award-info":[{"award-number":["2022YFC2702400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2700302"],"award-info":[{"award-number":["2021YFC2700302"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271720"],"award-info":[{"award-number":["82271720"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82288102"],"award-info":[{"award-number":["82288102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970797"],"award-info":[{"award-number":["31970797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The decidual endometrial stromal cells play a critical role in the establishment of uterine receptivity and pregnancy in human. Our previous studies demonstrate that protein tyrosine phosphatase 2 SHP2 is highly expressed in decidualized cells and governs the decidualization progress. However, the role and mechanism of SHP2 in the function of decidual cells remain unclear. Here, we screened proteins interacting with SHP2 in decidual hTERT-immortalized human endometrial stromal cells (T-HESCs) and identified Hypoxia-inducible factor-1 (HIF-1) signaling pathway as a potential SHP2-mediated signaling pathway through proximity-dependent biotinylation (BioID) analysis. Immunoprecipitation (Co-IP) revealed an interaction between SHP2 and HIF-1\u03b1, which colocalized to the nucleus in decidual cells. Furthermore, the SHP2 expression correlated with the transcriptional activation of HIF-1\u03b1 and its downstream genes Beta-enolase (Eno3), Pyruvate kinase 2 (Pkm2), Aldolase C (Aldoc), and Facilitative glucose transporter 1 (Glut1). Knockdown or inhibition of SHP2 significantly reduced the mRNA and protein levels of HIF-1\u03b1 and its downstream genes, as well as lactate production in decidual cells. We also established a hypoxia model of T-HESCs and 293\u00a0T cells and found that hypoxic treatment induced the expression of SHP2 and HIF-1\u03b1, which colocalized in the nucleus. SHP2 forced-expression rescued the inhibitory effects of SHP2 deficiency on HIF-1\u03b1 expression and lactate production. Finally, SHP2 binds to the promoter regions of HIF-1\u03b1 and its target genes (Eno3, Pkm2, Aldoc, and Glut1). Collectively, our results suggest that SHP2 influences the function of decidual cells by HIF-1\u03b1 signaling and provide a novel function mechanism of decidual stromal cells.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf019","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T16:51:20Z","timestamp":1738515080000},"page":"743-753","source":"Crossref","is-referenced-by-count":5,"title":["SHP2 regulates the HIF-1 signaling pathway in the decidual human endometrial stromal cells"],"prefix":"10.1093","volume":"112","author":[{"given":"Liqun","family":"Ouyang","sequence":"first","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Gao","sequence":"additional","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Cai","sequence":"additional","affiliation":[{"name":"Reproductive Medical Centre, The First Affiliated Hospital of Xiamen University , Zhenhai Road, Xiamen, Fujian 361005 ,","place":["China"]},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University , Xiangan South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingpu","family":"Tian","sequence":"additional","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Centre, The First Affiliated Hospital of Xiamen University , Zhenhai Road, Xiamen, Fujian 361005 ,","place":["China"]},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University , Xiangan South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangbo","family":"Kong","sequence":"additional","affiliation":[{"name":"Reproductive Medical Centre, The First Affiliated Hospital of Xiamen University , Zhenhai Road, Xiamen, Fujian 361005 ,","place":["China"]},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University , Xiangan South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxian","family":"Lu","sequence":"additional","affiliation":[{"name":"Xiamen City Key Laboratory of Metabolism, School of Pharmaceutical Sciences, Xiamen University , Xiangan South Road, Xiamen , Fujian 361102,","place":["China"]},{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University , Xiangan South Road, Xiamen, Fujian 361102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"2025041504315374500_ref1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2014-1045","article-title":"Cyclic decidualization of the human endometrium in reproductive health and failure","volume":"35","author":"Gellersen","year":"2014","journal-title":"Endocr Rev"},{"key":"2025041504315374500_ref2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242417616","article-title":"Molecular determinants of uterine receptivity: comparison of successful implantation, recurrent miscarriage, and recurrent implantation failure","volume":"24","author":"G\u00fcnther","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2025041504315374500_ref3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1071\/RD23119","article-title":"Understanding placentation in ruminants: a review focusing on cows and sheep","volume":"36","author":"Johnson","year":"2023","journal-title":"Reprod Fertil Dev"},{"key":"2025041504315374500_ref4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2021.09.012","article-title":"A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation","volume":"44","author":"Gurner","year":"2022","journal-title":"Reprod Biomed Online"},{"key":"2025041504315374500_ref5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000206024","article-title":"Pregnancy and autoimmunity","volume":"76","author":"Gleicher","year":"1986","journal-title":"Acta Haematol"},{"key":"2025041504315374500_ref6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1177\/1933719118802056","article-title":"Decidualization of human endometrial stromal fibroblasts is a multiphasic process involving distinct transcriptional programs","volume":"26","author":"Rytk\u00f6nen","year":"2019","journal-title":"Reprod Sci"},{"key":"2025041504315374500_ref7","doi-asserted-by":"crossref","first-page":"117731","DOI":"10.1016\/j.cca.2023.117731","article-title":"Non-coding RNAs in recurrent implantation failure","volume":"553","author":"Zahir","year":"2024","journal-title":"Clin Chim Acta"},{"key":"2025041504315374500_ref8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1203\/00006450-197604000-00006","article-title":"Lactate and pyruvate as fetal metabolic substrates","volume":"10","author":"Char","year":"1976","journal-title":"Pediatr Res"},{"key":"2025041504315374500_ref9","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1210\/en.2010-1266","article-title":"Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine 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endometrial decidualization","volume":"11","author":"Pinxiu Huang","year":"2022","journal-title":"Elife"},{"key":"2025041504315374500_ref29","article-title":"Biotin protein ligase as you like it: either extraordinarily specific or promiscuous protein biotinylation","volume":"92","author":"Cronan","year":"2023","journal-title":"Proteins"},{"key":"2025041504315374500_ref30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.7150\/ijms.88216","article-title":"Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: focus on pathological mechanism and pharmacological treatment","volume":"21","author":"Wan","year":"2024","journal-title":"Int J Med Sci"},{"key":"2025041504315374500_ref31","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.15252\/embr.201643300","article-title":"PKM2, cancer metabolism, and the road ahead","volume":"17","author":"Dayton","year":"2016","journal-title":"EMBO 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