{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T02:52:50Z","timestamp":1771037570226,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T00:00:00Z","timestamp":1485734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent evidence suggests that histone deacetylase inhibitors (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i) may mediate part of their antitumor effects by interfering with tumor angiogenesis. As signalling via the vascular endothelial growth factor receptor\u20102 (<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102) pathway is critical for angiogenic responses during tumor progression, we explored whether established antitumor effects of HDACi are partly mediated through diminished endothelial <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression. We therefore examined the potential impact of three different <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i, trichostatin A (<jats:styled-content style=\"fixed-case\">TSA<\/jats:styled-content>), sodium butyrate (But) and valproic acid (<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>), on <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 protein expression. <jats:styled-content style=\"fixed-case\">TSA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> VPA<\/jats:styled-content> and But significantly inhibit <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 protein expression in endothelial cells. Pertinent to these data, <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 protein half\u2010life is shown to be decreased in response to <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i. Recently, it could be demonstrated that expression of <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin influences <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 protein half\u2010life. In our experiments, <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 downregulation was accompanied by <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>i\u2010induced <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin suppression. Interestingly, si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated knockdown of <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin led to a pronounced loss of <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression on the protein as well as on the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> level, implicating that <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin not only influences <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 protein half\u2010life but also the transcriptional level. To further distinguish which of the eight different histone deacetylases are responsible for the regulation of <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression, specific <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> genes were silenced by transfecting respective si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s. These studies revealed that <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s 1, 4, 5 and 6 are preferentially involved in <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression. Therefore, these results provide an explanation for the anti\u2010angiogenic action of <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> inhibitors via a <jats:styled-content style=\"fixed-case\">VE<\/jats:styled-content>\u2010cadherin, <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content> 1 and <jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>s 4\u20136\u2010mediated suppression of <jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>\u20102 expression and might be of importance in the development of new anti\u2010angiogenic drugs.<\/jats:p>","DOI":"10.1111\/exd.13159","type":"journal-article","created":{"date-parts":[[2016,8,4]],"date-time":"2016-08-04T09:57:38Z","timestamp":1470304658000},"page":"194-201","source":"Crossref","is-referenced-by-count":37,"title":["Histone deacetylase inhibitors interfere with angiogenesis by decreasing endothelial <scp>VEGFR<\/scp>\u20102 protein half\u2010life in part via a <scp>VE<\/scp>\u2010cadherin\u2010dependent mechanism"],"prefix":"10.1111","volume":"26","author":[{"given":"Igor","family":"Hrgovic","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Pinter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Kippenberger","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Meissner","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Johann Wolfgang Goethe\u2010University  Frankfurt\/Main 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