Overexpression of the Flii gene increases dermal–epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita

• DOI: 10.1002/path.2973
• Publication Date: 2011-07-26T14:43:55Z
• Authors: Zlatko Kopecki; Ruth M Arkell; Xanthe L Strudwick; Misa Hirose; Ralf J Ludwig; Johannes S Kern; Leena Bruckner‐Tu...; Detlef Zillikens; Dedee F Murrell; Allison J Cowin
• Keywords: Epidermolysis bullosa acquisita; Haploinsufficiency

Abstract Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB still largely unknown and wound healing in patients suffering from remains major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator repair. Here we identify Flii novel target involved blistering. expression was significantly elevated 30 with EB, most prominently recessive dystrophic (RDEB) who defects production type VII collagen (ColVII). Using autoimmune ColVII murine model acquisita (EBA) immunocompetent‐ColVII‐hypomorphic mouse RDEB together alleles, investigated contribution EB. Overexpression produced blistering post‐induction EBA, while decreased reduced severity, integrin expression, improved production. +/− blistered showed α‐SMA, TGF‐β1, Smad 2/3 suggesting that decreasing may affect fibrosis. In support this, ‐deficient fibroblasts EBA mice were less able contract gels vitro ; however, addition TGF‐β1 restored contraction, interplay between TGF‐β1. Elevated gene further observed blisters hypomorphic mice, RDEB, reducing could be potential new approach for treating Copyright © 2011 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.