{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T17:42:34Z","timestamp":1740159754237,"version":"3.37.3"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Vascular Medicine"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p><jats:italic>Objective.<\/jats:italic>Endothelial tissue-type plasminogen activator (t-PA) release is a pivotal response to protect the circulation from occluding thrombosis. We have shown that the t-PA gene is epigenetically regulated and greatly induced by the histone deacetylase (HDAC) inhibitor valproic acid (VPA). We now investigated involvement of known t-PA promoter regulatory elements and evaluated dependence of potential interacting transcription factors\/cofactors.<jats:italic>Methods.<\/jats:italic>A reporter vector with an insert, separately mutated at either the t-PA promoter CRE or GC box II or GC box III elements, was transfected into HT-1080 and HUVECs and challenged with VPA. HUVECs were targeted with siRNA against histone acetyl transferases (HAT) and selected transcription factors from the Sp\/KLF family.<jats:italic>Results.<\/jats:italic>An intact VPA-response was observed with CRE mutated constructs, whereas mutation of GC boxes II and III reduced the magnitude of the induction by 54 and 79% in HT-1080 and 49 and 50% in HUVECs, respectively. An attenuated induction of t-PA mRNA was observed after Sp2, Sp4, and KLF5 depletion. KLF2 and p300 (HAT) were identified as positive regulators of basal t-PA expression and Sp4 and KLF9 as repressors.<jats:italic>Conclusion.<\/jats:italic>VPA-induced t-PA expression is dependent on the proximal GC boxes in the t-PA promoter and may involve interactions with Sp2, Sp4, and KLF5.<\/jats:p>","DOI":"10.1155\/2016\/7928681","type":"journal-article","created":{"date-parts":[[2016,2,7]],"date-time":"2016-02-07T21:00:50Z","timestamp":1454878850000},"page":"1-9","source":"Crossref","is-referenced-by-count":2,"title":["Dependence of Proximal GC Boxes and Binding Transcription Factors in the Regulation of Basal and Valproic Acid-Induced Expression of t-PA"],"prefix":"10.1155","volume":"2016","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6326-5175","authenticated-orcid":true,"given":"Erik","family":"Ulfhammer","sequence":"first","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Larsson","sequence":"additional","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Magnusson","sequence":"additional","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Karlsson","sequence":"additional","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niklas","family":"Bergh","sequence":"additional","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sverker","family":"Jern","sequence":"additional","affiliation":[{"name":"The Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00948.x"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000137380.91476.fb"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(05)61044-6"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00072.2005"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-6576.2008.01741.x"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.103.15.1936"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031573"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097260"},{"issue":"3","key":"9","volume":"10","year":"2015","journal-title":"PLoS ONE"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m101287200"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1042\/bj3100171"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr028"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1042\/bj2470605"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-012-0831-6"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.2.311"},{"issue":"24","key":"19","doi-asserted-by":"crossref","first-page":"14618","DOI":"10.1016\/S0021-9258(18)77347-X","volume":"265","year":"1990","journal-title":"Journal of Biological Chemistry"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)81080-6"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2580123.x"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1172\/jci107470"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.13.7167"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00942-4"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.01.094"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.4.5405"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.03.074"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.25.15320"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2008.08.027"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.24.4994"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000159707.05637.a1"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00058.2009"}],"container-title":["International Journal of Vascular Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijvm\/2016\/7928681.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijvm\/2016\/7928681.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijvm\/2016\/7928681.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T15:37:18Z","timestamp":1654270638000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.hindawi.com\/journals\/ijvm\/2016\/7928681\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016]]},"references-count":30,"alternative-id":["7928681","7928681"],"URL":"https:\/\/doi.org\/10.1155\/2016\/7928681","relation":{},"ISSN":["2090-2824","2090-2832"],"issn-type":[{"type":"print","value":"2090-2824"},{"type":"electronic","value":"2090-2832"}],"subject":[],"published":{"date-parts":[[2016]]}}}