Dermatopontin Expression is Decreased in Hypertrophic Scar and Systemic Sclerosis Skin Fibroblasts and is Regulated by Transforming Growth Factor-β1, Interleukin-4, and Matrix Collagen

Abstract

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.

Extracellular matrix dermatopontin modulates prostate cell growth in vivo

“…Fibrosis and keloids are associated with a decrease in the expression of dermatopontin and not an increase (Kuroda et al 1999, Catherino et al 2004. The discrepancy with the present data which indicate that overexpression of dermatopontin by tumor cells increased intratumoral stroma is unexplainable right now.…”

“…Leiomyomas and keloids demonstrated reduced levels of dermatopontin (Catherino et al 2004) and microarray analysis showed the downregulation of dermatopontin in leiomyoma compared with myometrium (Tsibris et al 2002). The decreased expression of dermatopontin is associated with the pathogenesis of fibrosis in hypertrophic scar and systemic sclerosis (Kuroda et al 1999). Additionally, stably transfected BALB/c 3T3 cells expressing mouse dermatopontin showed approximately 50% inhibition of cell proliferation (Tzen & Huang 2004).…”

Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology

“…The expression level of dermatopontin was reduced in hypertrophic scar and systemic sclerosis skin fibroblasts (Kuroda et al, 1999). Dermatopontin-null mice showed increased skin elasticity and reduced dermis thickness and skin collagen content, suggesting abnormal collagen fibrillogenesis (Takeda et al, 2002).…”

Expression profiling of senescent-associated genes in human dermis from young and old donors. Proof-of-concept study

“…This up-regulation of DPT found herein is not in agreement with data published on cultivated replicatively senescent human dermal fibroblasts (Yoon et al 2004). Interestingly, DPT mRNA and protein levels are up-regulated by TGF-β1 in non senescent fibroblasts (Kuroda et al 1999). Worth to note, DPT was also found to augment the biological activity of TGF-β1 ).…”