{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:44Z","timestamp":1772160704103,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neovascularization is a critical process in tumor progression and malignant transformation associated with neurofibromatosis type 1 (NF1). Indeed, fibroblasts are known to play a key role in the tumoral microenvironment modification by producing an abundant collagenous matrix, but their contribution in paracrine communication pathways is poorly understood. Here, we hypothesized that NF1 heterozygosis in human dermal fibroblasts could promote angiogenesis through exosomes secretion. The purposes of this study are to identify the NF1 fibroblast\u2010derived exosome protein contents and to determine their proangiogenic activity. Angiogenic proteome measurement confirmed the overexpression of VEGF and other proteins involved in vascularization. Tube formation of microvascular endothelial cells was also enhanced in presence of exosomes derived from NF1 skin fibroblasts. NF1 tissue\u2010engineered skin (NF1\u2010TES) generation showed a significantly denser microvessels networks compared to healthy controls. The reduction of exosomes production with an inhibitor treatment demonstrated a drastic decrease in blood vessel formation within the dermis. Our results suggest that NF1 haploinsufficiency alters the dermal fibroblast function and creates a pro\u2010angiogenic signal via exosomes, which increases the capillary formation. This study highlights the potential of targeting exosome secretion and angiogenesis for therapeutic interventions in NF1.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15982-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15982","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T02:21:44Z","timestamp":1697250104000},"page":"556-570","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heterozygous\n                    <scp>NF1<\/scp>\n                    dermal fibroblasts modulate exosomal content to promote angiogenesis in a\n                    <scp>tissue\u2010engineered<\/scp>\n                    skin model of neurofibromatosis type\u20101"],"prefix":"10.1111","volume":"167","author":[{"given":"Vincent","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Laval University  Quebec City Quebec Canada"},{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Paquet","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Laval University  Quebec City Quebec Canada"},{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Touzel\u2010Desch\u00eanes","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Laval University  Quebec City Quebec Canada"},{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne T.","family":"Khuong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Laval University  Quebec City Quebec Canada"},{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Dupr\u00e9","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"},{"name":"Department of Neurological Sciences, Faculty of Medicine Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3825-4885","authenticated-orcid":false,"given":"Francois","family":"Gros\u2010Louis","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine Laval University  Quebec City Quebec Canada"},{"name":"Division of Regenerative Medicine, CHU de Quebec Research Center Laval University  Quebec City Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2183"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1596016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2022.151997"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01103-4"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23433-0"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2022.109215"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3753-0_15"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14450"},{"key":"e_1_2_10_10_1","first-page":"6509","article-title":"Vascular innervation in benign neurofibromas of patients with neurofibromatosis type 1","volume":"35","author":"Friedrich R. 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