{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:16:00Z","timestamp":1769602560752,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T00:00:00Z","timestamp":1364256000000},"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":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurofibromatosis type I (<jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors (<jats:styled-content style=\"fixed-case\">MPNST<\/jats:styled-content>) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high\u2010level expression of vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> in neurofibromas remains unclear. In this study, we examined the effects of <jats:italic>Nf1<\/jats:italic> gene silencing on <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> expression in Schwann cell and non\u2010Schwann cell line and the upstream <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 \u2013 <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> pathway in Schwann cell line. The results indicated that <jats:italic>Nf1<\/jats:italic> gene silencing by lentiviral\u2010mediated <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> interference resulted in elevated expression of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> HIF<\/jats:styled-content>\u20101\u03b1 and phosphorylated <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> at the protein level. The results obtained from <jats:italic>Nf1<\/jats:italic> gene silencing in murine Schwann cell line analogously suggest that <jats:italic>NF1<\/jats:italic> gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> expression without the tumor microenvironment by activation of the <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 \u2013 <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> pathway. We also showed that interleukin\u20106 is upregulated in <jats:italic>Nf1<\/jats:italic> gene knock\u2010down Schwann cells at the protein level.<\/jats:p>","DOI":"10.1111\/exd.12115","type":"journal-article","created":{"date-parts":[[2013,2,11]],"date-time":"2013-02-11T07:50:47Z","timestamp":1360569047000},"page":"262-265","source":"Crossref","is-referenced-by-count":26,"title":["<i><scp>NF<\/scp>1<\/i> gene silencing induces upregulation of vascular endothelial growth factor expression in both Schwann and non\u2010Schwann cells"],"prefix":"10.1111","volume":"22","author":[{"given":"Yasuhiro","family":"Kawachi","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Maruyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Ishitsuka","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Furuta","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiko","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minao","family":"Furumura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine Shimane University Izumo Shimane Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fujio","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine University of Tsukuba Tennodai Tsukuba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90024-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90149-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/356713a0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1752"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2003.00062.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9279-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-008-9197-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00245-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/01913129109016243"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.2.010506.091940"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(02)00078-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210261"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2010.01237.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1172\/JCI19195","volume":"112","author":"Yang F C","year":"2003","journal-title":"J Clin Invest"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","unstructured":"Riccardi V M. 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