{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:40:31Z","timestamp":1790365231051,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":257,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81741047"],"award-info":[{"award-number":["81741047"]}],"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":["82101785"],"award-info":[{"award-number":["82101785"]}],"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":["82101786"],"award-info":[{"award-number":["82101786"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Preeclampsia is regarded as an evolution\u2010related disease that has only been observed in humans and our closest relatives, and the important factor contributing to its pathogenesis is endothelial dysregulation secondary to a stressed placenta. Hypoxia\u2010inducible factor 1 subunit alpha (HIF1<jats:italic>\u03b1<\/jats:italic>), a highly conserved molecule in virtually all mammals, is regarded as a crucial regulator of the hypoxia adaptation and evolution. Persistent high expression of HIF1<jats:italic>\u03b1<\/jats:italic> in the placenta is one of the pathogenic mechanisms of preeclampsia. Therefore, human\u2010specific molecules should link increased HIF1<jats:italic>\u03b1<\/jats:italic> to preeclampsia. We reported that urothelial cancer associated 1 (UCA1) is a potential mediator because it is a human\u2010specific long noncoding RNA (lncRNA) that is upregulated in placental tissues and maternal serum from women with preeclampsia and is regulated by HIF1<jats:italic>\u03b1<\/jats:italic>. The cellular HIF1<jats:italic>\u03b1<\/jats:italic>\u2010UCA1 pathway promoted the adaptation of trophoblasts to hypoxia by inducing vascular endothelial growth factor (VEGF) secretion and changes in the levels of key enzymes in glycolysis. On the other hand, circulating exosomal UCA1 secreted from stressed trophoblasts induced vascular endothelial dysfunction, especially excess ROS production, as measured by exosome extraction and a coculture system. At the molecular level, UCA1 physically bound to ubiquitin\u2010specific peptidase 14 (USP14), which is a deubiquitinating enzyme, and UCA1 functioned as a scaffold to recruit USP14 to profilin 1 (PFN1), an actin\u2010binding protein contributing to endothelial abnormalities and vascular diseases. This ternary complex inhibited the ubiquitination\u2010dependent degradation of PFN1 and prolonged its half\u2010life, further activating the RhoA\/Rho\u2010kinase (ROCK) pathway to induce ROS production in endothelial cells. Taken together, these observations suggest a role for the evolution\u2010related UCA1 in the HIF1<jats:italic>\u03b1<\/jats:italic>\u2010induced adaptive pathogenic mechanism of preeclampsia, promoting the survival of hypoxic trophoblasts and injuring maternal endothelial cells.<\/jats:p>","DOI":"10.1155\/2022\/2198923","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T21:50:07Z","timestamp":1663278607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Trophoblast Exosomal UCA1 Induces Endothelial Injury through the PFN1\u2010RhoA\/ROCK Pathway in Preeclampsia: A Human\u2010Specific Adaptive Pathogenic Mechanism"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-6480","authenticated-orcid":false,"given":"Suwen","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5929-5101","authenticated-orcid":false,"given":"Yutong","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3664-8031","authenticated-orcid":false,"given":"Huanqiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2808-2314","authenticated-orcid":false,"given":"Xirong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-9145","authenticated-orcid":false,"given":"Lili","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-8790","authenticated-orcid":false,"given":"Huangfang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-161X","authenticated-orcid":false,"given":"Qiongjie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3089-0967","authenticated-orcid":false,"given":"Duan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2051-4581","authenticated-orcid":false,"given":"Xiaotian","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dml016"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2010.10.010"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2009.02.010"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f6564"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2013.05.005"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.10.005"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-677"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8316"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.9.3300"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp046"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l2381"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semperi.2014.03.005"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0078"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0893"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39426-5"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.05314"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-018-9870-8"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.11.004"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102813"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2016_350"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0714-8"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103580"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.12.009"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703227200"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-12-141"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4169575"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23247"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.08.013"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01970-8"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29660-3"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-1925-x"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2018.6182"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06883-x"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201903630"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2018.04.030"},{"key":"e_1_2_14_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.10.047"},{"key":"e_1_2_14_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.633937"},{"key":"e_1_2_14_38_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-019-0341-8"},{"key":"e_1_2_14_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00794.2005"},{"key":"e_1_2_14_40_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-00672"},{"key":"e_1_2_14_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2018.08.004"},{"key":"e_1_2_14_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12707"},{"key":"e_1_2_14_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09321"},{"key":"e_1_2_14_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00608"},{"key":"e_1_2_14_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24392"},{"key":"e_1_2_14_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-020-03214-9"},{"key":"e_1_2_14_47_2","doi-asserted-by":"publisher","DOI":"10.1136\/oem.58.10.619"},{"key":"e_1_2_14_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-016-2405-0"},{"key":"e_1_2_14_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2012.06.009"},{"key":"e_1_2_14_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0753-3"},{"key":"e_1_2_14_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-020-10039-0"},{"key":"e_1_2_14_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000437382.03963.88"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2198923.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/2198923.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/2198923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T01:48:56Z","timestamp":1748915336000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/2198923"}},"subtitle":[],"editor":[{"given":"Junmin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/2198923"],"URL":"https:\/\/doi.org\/10.1155\/2022\/2198923","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2022-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2198923"}}