TRANSFORMING GROWTH-FACTOR-BETA REVERSES DEFICIENT EXPRESSION OF TYPE-(I) COLLAGEN IN CULTURED FIBROBLASTS OF A PATIENT WITH METAGERIA

Metageria is a generalized form of acrogeria belonging to the group of premature aging syndromes and is characterized by loss of subcutaneou s fat, thinning of the dermis, multiple teleangiectasias and mottled h yperpigmentation. The skin changes present suggest that an altered for mation of extracellular matrix might be involved in the pathogenesis o f this disease. Fibroblasts obtained from the skin of a patient with t his 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 fibronec tin mRNA levels were found. Similar although less pronounced changes w ere observed in fibroblasts obtained from the sister of this patient s howing 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 o f the cells with transforming growth factor-beta, a strong inducer of type I collagen and extracellular matrix formation, restored type I co llagen expression both at the mRNA and protein level to amounts compar able with normal skin fibroblasts. These results are consistent with a defect in type I collagen transcription that is readily reversed afte r incubation with transforming growth factor beta. The deficient synth esis of type I collagen and decorin by dermal fibroblasts might thus c ontribute to an altered formation of the extracellular matrix resultin g in the poikilodermic skin changes observed in this patient.