{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T07:19:42Z","timestamp":1776496782950,"version":"3.51.2"},"reference-count":87,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>Persistent hypoxia and inflammation beyond early pregnancy are involved in a bad outcome because of defective trophoblast invasiveness. Tissue transglutaminase (TG2) coregulates several cell functions. An aberrant expression and\/or transamidation activity could contribute to placental dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>The first\u2010trimester trophoblast cell line (Swan\u201071) was used to study TG2 expression and cell functions in the absence or presence of inflammatory cytokines (TNF\u2010\u03b1, IL\u20101\u03b2) or chemical hypoxia (CoCl<jats:sub>2<\/jats:sub>). We analyzed The concentration of cytokines in the supernatant by ELISA; Cell migration by scratch assay; NF\u2010\u03baB activation by detection of nuclear p65 by immunofluorescence or flow cytometry using a Swan\u201071 NF\u2010\u03baB\u2010hrGFP reporter cell line. Tissue transglutaminase expression was analyzed by immunoblot and confocal microscopy. Expression of spliced mRNA variants of tissue transglutaminase was analyzed by RT\u2010PCR. Transamidation activity was assessed by flow cytometry using 5\u2010(biotinamido)\u2010pentylamine substrate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chemical hypoxia and TGase inhibition, but not inflammatory stimuli, decreased Swan\u201071 migration. IL\u20106 production was also decreased by chemical hypoxia, but increased by inflammation. Intracellular TGase activity was increased by all stimuli, but NF\u2010\u03baB activation was observed only in the presence of proinflammatory cytokines. TG2 expression was decreased by CoCl<jats:sub>2<\/jats:sub>and TNF\u2010\u03b1. Translocation of TG2 and p65 to nuclei was observed only with TNF\u2010\u03b1, without colocalization. Differential relative expression of spliced variants of mRNA was observed between CoCl<jats:sub>2<\/jats:sub>and inflammatory stimuli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The observed decrease in total TG2 expression and relative increase in short variants under hypoxia conditions could contribute to impaired trophoblast invasion and impact on pregnancy outcome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13534","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T13:49:56Z","timestamp":1646747396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hypoxia and inflammation conditions differentially affect the expression of tissue transglutaminase spliced variants and functional properties of extravillous trophoblast cells"],"prefix":"10.1111","volume":"87","author":[{"given":"Paula","family":"Arbildi","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Facultad de Ciencias\/Facultad de Qu\u00edmica Universidad de la Rep\u00fablica, Instituto de Higiene Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Rodr\u00edguez\u2010Camejo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Facultad de Ciencias\/Facultad de Qu\u00edmica Universidad de la Rep\u00fablica, Instituto de Higiene Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Perelmuter","sequence":"additional","affiliation":[{"name":"Cell Biology Unit Institut Pasteur de Montevideo Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariela","family":"Bollati\u2010Fogol\u00edn","sequence":"additional","affiliation":[{"name":"Cell Biology Unit Institut Pasteur de Montevideo Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"S\u00f3\u00f1ora","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Facultad de Ciencias\/Facultad de Qu\u00edmica Universidad de la Rep\u00fablica, Instituto de Higiene Montevideo Uruguay"},{"name":"Escuela Universitaria de Tecnolog\u00eda M\u00e9dica (EUTM)\u2010Facultad de Medicina Hospital de Cl\u00ednicas Universidad de la Rep\u00fablica Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-0208","authenticated-orcid":false,"given":"Ana","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Facultad de Ciencias\/Facultad de Qu\u00edmica Universidad de la Rep\u00fablica, Instituto de Higiene Montevideo Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.082764gb"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.11.018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.1999.0522"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.08.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-09-0598"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2014.102"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00070-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2012.01.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3864941"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2004.02.011"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2011-0645-RA"},{"issue":"6","key":"e_1_2_8_13_1","first-page":"2484","article-title":"HIF\u20101\u03b1 affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions","volume":"21","author":"Zhang Z","year":"2020","journal-title":"Mol Med Rep"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641955.2011.642436"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12290"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(02)02182-5"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2013"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042454899"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-1127-4"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08345.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2741\/4117"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2011.09.012"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.6.3724"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041364"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-017-2394-5"},{"issue":"2","key":"e_1_2_8_27_1","first-page":"19","article-title":"The Role of Tissue Transglutaminase in Cancer Cell Initiation, Survival and Progression","volume":"7","author":"Tabolacci C","year":"2019","journal-title":"Med Sci"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.342"},{"issue":"2","key":"e_1_2_8_29_1","first-page":"G240","article-title":"TNF\u2010alpha modulates expression of the tissue transglutaminase gene in liver cells","volume":"274","author":"Kuncio GS","year":"1998","journal-title":"Am J Physiol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12659"},{"issue":"4","key":"e_1_2_8_31_1","first-page":"108","article-title":"Differential Expression of Tissue Transglutaminase Splice Variants in Peripheral Blood Mononuclear Cells of Primary Progressive Multiple Sclerosis Patients","volume":"6","author":"Sestito C","year":"2018","journal-title":"Med Sci"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.3.8603579"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.01.008"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199701)181:1<106::AID-PATH725>3.0.CO;2-K"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0240"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394305-7.00001-X"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.061747"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02361"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.09.080"},{"issue":"1","key":"e_1_2_8_40_1","first-page":"3","article-title":"Celiac disease and its effect on human reproduction: a review","volume":"55","author":"Soni S","year":"2010","journal-title":"J Reprod Med"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2012.01.007"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-7-16"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2011.01020.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2013.11.001"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513810701563637"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.08.007"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2019.05.014"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/860534"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000430181"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot087288"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0722.2012.00949.x"},{"issue":"24","key":"e_1_2_8_52_1","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1242\/jcs.175968","article-title":"P2X7 receptor activation regulates rapid unconventional export of transglutaminase\u20102","volume":"128","author":"Adamczyk M","year":"2015","journal-title":"J Cell Sci"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001967"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac503130v"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101376"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.30"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(99)00118-9"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.11.2901"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.08.009"},{"issue":"3","key":"e_1_2_8_61_1","first-page":"1508","article-title":"Hypoxia\u2010induced expression of CXCR4 favors trophoblast cell migration and invasion via the activation of HIF\u20101\u03b1","volume":"42","author":"Zhang Z","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2009.00778.x"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/5.11.1055"},{"issue":"5","key":"e_1_2_8_64_1","first-page":"1582","article-title":"Hypoxia Stimulates Cytokine Production by Villous Explants from the Human Placenta 1","volume":"82","author":"Benyo DF","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.01.013"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.06.023"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.099937"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127009"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.09.048"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049266z"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808331200"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.148.4.825"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-06-0549"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041490304"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00175a024"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.17.9748"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61682-3"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019414"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1457"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407627200"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08409.x"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells5010010"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.699108"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00850.x"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.01.050"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(01)00062-6"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503323200"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-016-2296-y"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13534","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aji.13534","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13534","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T22:36:15Z","timestamp":1726785375000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,14]]},"references-count":87,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1111\/aji.13534"],"URL":"https:\/\/doi.org\/10.1111\/aji.13534","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,14]]},"assertion":[{"value":"2021-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13534"}}