Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen.
Dermatopontin is a recently discovered extracellular matrix protein with proteoglycan and cell-binding properties and is assumed to play important roles in cell-matrix interactions and matrix assembly. In this study we examined the expression of dermatopontin mRNA and protein in skin fibroblast cultures from patients with hypertrophic scar and patients with systemic sclerosis. Dermatopontin mRNA and protein levels were reduced in fibroblast cultures from hypertrophic scar lesional skin compared with fibroblasts from normal skin of the same hypertrophic scar patient. Fibroblast cultures from systemic sclerosis patient involved skin also showed significantly reduced expression of dermatopontin compared with normal skin fibroblasts from healthy individuals. We also investigated the effects of cytokines and matrix collagen on dermatopontin expression in normal cultured fibroblasts. Transforming growth factor-beta1 increased dermatopontin mRNA and protein levels, while interleukin-4 reduced dermatopontin expression. Substrate coated with type I collagen reduced dermatopontin mRNA levels, the reduction being more prominent in three-dimensional collagen matrices. Our results suggest that the decreased expression of dermatopontin is associated with the pathogenesis of fibrosis in hypertrophic scar and systemic sclerosis, and that the effect of the cytokines and matrix collagen on dermatopontin may have important implications for skin fibrosis.
Kuroda
K
K
Department of Dermatology, School of Medicine, Chiba University, Chiba, Japan.
Okamoto
O
O
Shinkai
H
H
D000293:Adolescent; D000328:Adult; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans; D017439:Cicatrix, Hypertrophic / Q000378:metabolism*; D003094:Collagen / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D003094:Collagen