Werner's syndrome. Evidence for preferential regional expression of a generalized mesenchymal cell defect.
We describe a patient with Werner's syndrome from whom skin biopsy specimens were sampled for histology and electron microscopy and fibroblasts were cultured. Tissue sampled from five sites that varied in clinical presentation revealed striking changes in the dermoepidermal junction, elastic fibers of the papillary and reticular dermis, and adipose tissue of the hypodermis. The density and organization of the collagenous connective tissue was altered variably depending on the biopsy site. Changes noted in the epidermis were indicative of tissue regeneration and repair. Cells derived from acral areas grew poorly and could not be passed. Collagen synthesis in these cells was enhanced approximately 50%, and collagenase expression was decreased to a similar degree. Cells derived from the skin of the trunk could be passed but had an abbreviated in vitro life span. Collagen synthesis in these cells was unaltered. Serum from the patient with Werner's syndrome or from his obligate heterozygote offspring stimulated collagen synthesis in low-passage normal human skin fibroblast target cells. Sequential passage of these normal cells resulted in a blunting of the stimulatory effect. These observations suggest that a stimulator of collagen synthesis exists in the serum of patients with Werner's syndrome and that as cells (either normal or Werner's syndrome) "age" in vitro they may become hyporesponsive to this as yet undefined stimulatory factor in serum.
Bauer
E A
EA
Division of Dermatology, Washington University School of Medicine, St Louis, MO 63110.
Uitto
J
J
Tan
E M
EM
Holbrook
K A
KA
D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011347:Procollagen / Q000096:biosynthesis; D014898:Werner Syndrome / Q000473:pathology / Q000503:physiopathology*
D011347:Procollagen; D003094:Collagen