{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:45:00Z","timestamp":1788795900052,"version":"build-2803163510"},"reference-count":180,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The \u03b1v\u03b23 integrin, an endothelial cells\u2019 receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical \u03b15\u03b21 integrin receptor, whereas the \u03b1v\u03b23 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the \u03b1v\u03b23 integrin, due to the lack of FN\u2013ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers\u2013Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the \u03b1v\u03b23 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, \u03b1v\u03b23 rescues patients\u2019 fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the \u03b1v\u03b23 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical \u03b1v\u03b23 integrin-TGFBRII signaling, involving p125FAK\/p60Src\/p38MAPK. The characterization of these different biological functions triggered by \u03b1v\u03b23 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.<\/jats:p>","DOI":"10.3390\/ijms19040982","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T03:43:29Z","timestamp":1522035809000},"page":"982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Multifaced Roles of the \u03b1v\u03b23 Integrin in Ehlers\u2013Danlos and Arterial Tortuosity Syndromes\u2019 Dermal Fibroblasts"],"prefix":"10.3390","volume":"19","author":[{"given":"Nicoletta","family":"Zoppi","sequence":"first","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Chiarelli","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7025-2495","authenticated-orcid":false,"given":"Marco","family":"Ritelli","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3624-2354","authenticated-orcid":false,"given":"Marina","family":"Colombi","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1126\/science.1176009","article-title":"The extracellular matrix: Not just pretty fibrils","volume":"326","author":"Hynes","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1242\/jcs.023820","article-title":"The extracellular matrix at a glance","volume":"123","author":"Frantz","year":"2010","journal-title":"J. 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