title: Transforming growth factor-beta reverses deficient expression of type (I) collagen in cultured fibroblasts of a patient with metageria.
abstract: Metageria is a generalized form of acrogeria belonging to the group of premature aging syndromes and is characterized by loss of subcutaneous fat, thinning of the dermis, multiple teleangiectasias and mottled hyperpigmentation. The skin changes present suggest that an altered formation of extracellular matrix might be involved in the pathogenesis of this disease. Fibroblasts obtained from the skin of a patient with this disease revealed a marked reduction of type I collagen expression to about 20% of control levels both at the mRNA and protein level. In addition decreased decorin but unchanged type IV collagen and fibronectin mRNA levels were found. Similar although less pronounced changes were observed in fibroblasts obtained from the sister of this patient showing skin changes compatible with acrogeria. To further analyze the deficient expression of type I collagen run on analysis was performed revealing a decrease of transcription of type I collagen. Incubation of the cells with transforming growth factor-beta, a strong inducer of type I collagen and extracellular matrix formation, restored type I collagen expression both at the mRNA and protein level to amounts comparable with normal skin fibroblasts. These results are consistent with a defect in type I collagen transcription that is readily reversed after incubation with transforming growth factor beta. The deficient synthesis of type I collagen and decorin by dermal fibroblasts might thus contribute to an altered formation of the extracellular matrix resulting in the poikilodermic skin changes observed in this patient.
authors.affiliation: Department of Dermatology, University of Cologne, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Hunzelmann
authors.forename: U
authors.initials: U
authors.lastname: Ueberham
authors.forename: B
authors.initials: B
authors.lastname: Eckes
authors.forename: K
authors.initials: K
authors.lastname: Herrmann
authors.forename: T
authors.initials: T
authors.lastname: Krieg
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014898:Werner Syndrome / Q000378:metabolism*
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen