title: Recessive dystrophic epidermolysis bullosa keratinocytes synthesize type VII collagen alpha chains of normal molecular size but the anchoring fibril assembly is impaired.
abstract: Recessive dystrophic epidermolysis bullosa is a blistering skin disease characterized by diminished anchoring fibrils within the cutaneous basement membrane zone. Because anchoring fibrils are composed of type VII collagen, we compared the synthesis of type VII collagen by keratinocytes from patients and normal subjects. By Western blot analysis and immunoprecipitation of cell extracts, we found that both cell types express type VII collagen alpha chains of equivalent size (Mr = 290,000). Transforming growth factor-beta enhanced type VII collagen in both cell types. In contrast, the expression of type VII collagen within the culture medium was markedly diminished or absent in cultures of keratinocytes from patients. The patients' keratinocytes are capable of synthesizing type VII collagen of a normal molecular size, but they cannot assemble or secrete type VII collagen properly into the extracellular space, or they secrete a product that is abnormally sensitive to proteolytic digestion.
authors.affiliation: Department of Dermatology, Northwestern University Medical School, Chicago, IL 60611.
authors.forename: T
authors.initials: T
authors.lastname: Iwasaki
authors.forename: J C
authors.initials: JC
authors.lastname: Lapiere
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: D T
authors.initials: DT
authors.lastname: Woodley
mesh_terms: D001485:Basement Membrane / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005808:Genes, Recessive; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D046911:Macromolecular Substances; D008970:Molecular Weight; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012016:Reference Values; D012867:Skin / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D012313:RNA; D003094:Collagen