Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor-beta.
Keratinocytes and fibroblasts derived from skin of a patient with recessive dystrophic mutilating epidermolysis bullosa (EB) did not synthesize collagen VII as assessed by indirect immunofluorescence staining or immunoblotting, but expressed another basement membrane protein, laminin, in a normal manner. In contrast to control cells, no stimulation of collagen VII production was achieved in co-cultures of EB keratinocytes and fibroblasts. Further, treatment of normal keratinocytes or co-cultures with TGF-beta 2 significantly increased their expression of collagen VII, whereas the cytokine failed to induce its synthesis in the EB cells. Mixed co-cultures were constructed with normal fibroblasts and EB keratinocytes and vice versa. Both combinations showed strong expression of collagen VII in the normal cells but no synthesis in the EB counterparts. These results suggest that in this patient with severe mutilating dystrophic EB, inability of cutaneous cells to synthesize sufficient amounts of collagen VII underlies the lack of anchoring fibrils and skin fragility.
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D016108:Epidermolysis Bullosa Dystrophica / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism*; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D003094:Collagen