Werner's syndrome. Evidence for preferential regional expression of a generalized mesenchymal cell defect

Bauer, Eugene A.; Uitto, Jouni; Tan, Elaine M.L.; Holbrook, Karen A.

doi:10.1001/archderm.124.1.90

Cited by 13 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Werner's syndrome has been considered to represent premature aging, and fibroblasts from patients with the disease have been studied in an attempt to understand the molecular mechanisms that induce aging. It has been pointed out, however, that Werner's syndrome causes skin changes more typical of scleroderma than those resulting from normal aging (Takeda et al, 1987;Bauer et al, 1988). In agreement with this view are the observations that in Werner's syndrome fibroblasts, the rates of synthesis of collagen and glycosaminoglycan were increased (Takeda et al, 1987;Arakawa et al, 1990) as were the steady-state levels of mRNA for al(I), a2(I), and al(II1) collagen chains (Arakawa et al, 1990;Murano et al, 19911, compared to age-matched controls.…”

Section: Discussionmentioning

confidence: 99%

Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts

Takeda

Gosiewska

Peterkofsky

1992

Journal Cellular Physiology

View full text Add to dashboard Cite

Regulation of the synthesis of procollagen and other extracellular matrix components was examined in human skin fibroblasts obtained from donors of various ages, from fetal to 80 years old (in vivo aged), and in fetal fibroblasts at varying passage levels (in vitro aged). Growth rates and saturation densities of fibroblasts decreased with increasing age of the donor and after passage 20 of fetal fibroblasts. The rates of collagen and proteoglycan synthesis also decreased during both types of aging to about 10-25% of the rate in early passage fetal fibroblasts, whereas the synthesis of total noncollagenous proteins was not greatly affected. Decreased collagen synthesis in both types of aging was correlated with lower steady-state levels of mRNAs for the two subunits of type I procollagen mRNA, although their regulation was not coordinate. Type III collagen mRNA levels also declined in both types of aging. The concentration of fibronectin mRNA also decreased during in vitro aging but more rapidly than the collagen mRNAs, whereas in fibroblasts from 51-80-year-old donors, it was similar to or higher than in early passage fetal fibroblasts. This study suggests that the decreased synthesis of procollagen and proteoglycans in in vivo aged fibroblasts represents changes that are responsible for intrinsic degenerative changes that occur in human skin during aging. Furthermore, although in vitro and in vivo aging were similar in many respects, they were not equivalent, as evidenced by the differences in regulation of fibronectin expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts

Takeda

Gosiewska

Peterkofsky

1992

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…8 A wide variety of tumors have been reported to occur in patients with Werner's syndrome. 1 Thirteen of the 125 cases (10%) reviewed by these • authors had predominantly mesenchymal tumors.…”

Section: Discussionmentioning

confidence: 99%