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Differentially expressed proteins (DEPs) in plasma of patients experiencing RSA is helpful to find new therapeutic targets and identified with mass spectrometry. In 57 DEPs, 21 were upregulated and 36 were downregulated in RSA. Gene ontology analyses indicated that identified DEPs were associated with cell proliferation, including significantly downregulated insulin\u2010like growth factor binding protein 2 (IGFBP2). Immunohistochemical result using clinical decidual tissues also showed that IGFBP2 expression was significantly decreased in RSA trophoblasts. Cell proliferation assay indicated that IGFBP2 treatment increased the proliferation and mRNA expressions of PCNA and Ki67 in trophoblast cells. Transcriptome sequencing experiments and Kyoto Encyclopedia of Genes and Genomes analyses revealed that gene expression for components in PI3K\u2010Akt pathway in trophoblasts was significantly upregulated following IGFBP2 treatment. To confirm bioinformatics findings, we did cell\u2010based experiments and found that treatment of inhibitors for insulin\u2010like growth factor (IGF)\u20101 receptor\u2010PI3K\u2010Akt pathway significantly reduced IGFBP2\u2010induced trophoblast cell proliferation and mRNA expressions of PCNA and Ki67. Our findings suggest that IGFBP2 may increase trophoblast proliferation through the PI3K\u2010Akt signaling pathway to affect pregnancy outcomes and that IGFBP2 may be a new target for future research and treatment of RSA.<\/jats:p>","DOI":"10.14814\/phy2.15939","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T09:28:17Z","timestamp":1707298097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Role of increased <scp>IGFBP2<\/scp> in trophoblast cell proliferation and recurrent spontaneous abortion development: A pilot study"],"prefix":"10.14814","volume":"12","author":[{"given":"Li","family":"Ji","sequence":"first","affiliation":[{"name":"The First Clinical Medical College Nanjing University of Traditional Chinese Medicine  Nanjing China"},{"name":"Department of Obstetrics and Gynecology Lu'an Traditional Chinese Hospital, The Affiliated Hospital of Anhui University of Chinese Medicine  Lu'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Jiao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Wan","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College Nanjing University of Traditional Chinese Medicine  Nanjing China"},{"name":"Department of Gynecology The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunzhi","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Lu'an Traditional Chinese Hospital, The Affiliated Hospital of Anhui University of Chinese Medicine  Lu'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7263-4748","authenticated-orcid":false,"given":"Bing","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Sciences Anhui Medical University  Hefei China"},{"name":"Dr. Neher\u2019s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology  Macau China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College Nanjing University of Traditional Chinese Medicine  Nanjing China"},{"name":"Department of Gynecology The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Spontaneous abortion","author":"Alves C.","year":"2023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.11.8895319"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt0816-888d"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-23-0224"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2019.1656755"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1071\/RD22123"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.6425"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2001-0033"},{"key":"e_1_2_10_12_1","first-page":"1243","article-title":"Management of spontaneous abortion","volume":"72","author":"Griebel C. 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