{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T07:23:49Z","timestamp":1792740229579,"version":"4.5.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,9,26]],"date-time":"2011-09-26T00:00:00Z","timestamp":1316995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair. Here we identify Flii as a novel target involved in skin blistering. Flii expression was significantly elevated in 30 patients with EB, most prominently in patients with recessive dystrophic EB (RDEB) who have defects in production of type VII collagen (ColVII). Using an autoimmune ColVII murine model of EB acquisita (EBA) and an immunocompetent\u2010ColVII\u2010hypomorphic genetic mouse model of RDEB together with murine\n                    <jats:italic>Flii<\/jats:italic>\n                    alleles, we investigated the contribution of\n                    <jats:italic>Flii<\/jats:italic>\n                    to EB. Overexpression of\n                    <jats:italic>Flii<\/jats:italic>\n                    produced severe blistering post\u2010induction of EBA, while decreased\n                    <jats:italic>Flii<\/jats:italic>\n                    reduced blister severity, elevated integrin expression, and improved ColVII production.\n                    <jats:italic>Flii<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    blistered skin showed reduced \u03b1\u2010SMA, TGF\u2010\u03b21, and Smad 2\/3 expression, suggesting that decreasing Flii may affect fibrosis. In support of this,\n                    <jats:italic>Flii<\/jats:italic>\n                    \u2010deficient fibroblasts from EBA mice were less able to contract collagen gels\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; however, addition of TGF\u2010\u03b21 restored collagen contraction, suggesting an interplay between Flii and TGF\u2010\u03b21. Elevated\n                    <jats:italic>Flii<\/jats:italic>\n                    gene and protein expression was further observed in the blisters of ColVII hypomorphic mice, a murine model of RDEB, suggesting that reducing Flii in blistered skin could be a potential new approach for treating patients with EB. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2973","type":"journal-article","created":{"date-parts":[[2011,7,26]],"date-time":"2011-07-26T10:43:55Z","timestamp":1311677035000},"page":"401-413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Overexpression of the\n                    <i>Flii<\/i>\n                    gene increases dermal\u2013epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita"],"prefix":"10.1002","volume":"225","author":[{"given":"Zlatko","family":"Kopecki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth M","family":"Arkell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xanthe 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