title: Topical application of recombinant type VII collagen incorporates into the dermal-epidermal junction and promotes wound closure.
abstract: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and skin wounds due to mutations in the gene that codes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. In this study, we evaluated if topically applied human recombinant C7 (rC7) could restore C7 at the dermal-epidermal junction (DEJ) and enhance wound healing. We found that rC7 applied topically onto murine skin wounds stably incorporated into the newly formed DEJ of healed wounds and accelerated wound closure by increasing re-epithelialization. Topical rC7 decreased the expression of fibrogenic transforming growth factor-β2 (TGF-β2) and increased the expression of anti-fibrogenic TGF-β3. These were accompanied by the reduced expression of connective tissue growth factor, fewer α smooth muscle actin (α-SMA)-positive myofibroblasts, and less deposition of collagen in the healed neodermis, consistent with less scar formation. In addition, using a mouse model in which skin from C7 knock out mice was grafted onto immunodeficient mice, we showed that applying rC7 onto RDEB grafts with wounds restored C7 and anchoring fibrils (AFs) at the DEJ of the grafts and corrected the dermal-epidermal separation. The topical application of rC7 may be useful for treating patients with RDEB and patients who have chronic skin wounds.
authors.affiliation: Department of Dermatology, University of Southern California, Los Angeles, California, USA.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.forename: Pedram
authors.initials: P
authors.lastname: Ghasri
authors.forename: Mahsa
authors.initials: M
authors.lastname: Amir
authors.forename: Brian
authors.initials: B
authors.lastname: Hwang
authors.forename: Yingpin
authors.initials: Y
authors.lastname: Hou
authors.forename: Michael
authors.initials: M
authors.lastname: Khalili
authors.forename: Michael
authors.initials: M
authors.lastname: Khilili
authors.forename: Andrew
authors.initials: A
authors.lastname: Lin
authors.forename: Douglas
authors.initials: D
authors.lastname: Keene
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: David T
authors.initials: DT
authors.lastname: Woodley
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D024143:Collagen Type VII / Q000008:administration & dosage / Q000627:therapeutic use*; D020405:Dermis / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D016108:Epidermolysis Bullosa Dystrophica / Q000188:drug therapy; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D024143:Collagen Type VII; D011994:Recombinant Proteins