Analysis of Gene Expression Patterns in Human Postburn Hypertrophic Scars

Abstract

Hypertrophic scars cause cosmetic disfigurement and limited mobility in burn patients. To better understand the molecular pathophysiology of hypertrophic scar formation, microarray analyses were performed on normal skin and hypertrophic scars from four burn patients. Microarray analyses were determined in an effort to identify genes whose expression discriminated between normal skin and mature, hypertrophic scars. Surgical biopsies were obtained from two pediatric and two adult patients 6 to 15 months after burn injury. Total RNA was isolated from the samples and subjected to microarray analysis using the Affymetrix U95Av2 GeneChip. Results from this analysis revealed 31 probe sets representing genes that were consistently up-regulated at least two-fold in hypertrophic scar specimens from all four patients and four probe sets that were down-regulated. The significance analysis of microarrays algorithm also identified 35 probe sets whose increased expression resulted in the hierarchal clustering of the hypertrophic scar and normal tissue, seven of which were identical to the six genes identified by paired analyses. These six genes all displayed elevated levels of expression in the scar tissue. Proteins encoded by the genes identified included germline oligometric matrix protein, matrix metalloproteinase-16, collagen type 1alpha, pleiotrophin, and thrombospondin-4. Although the results presented here suggest that there may be unique patterns of gene expression in hypertrophic scars that may be important in the evaluation and treatment of hypertrophic scarring, the results must be confirmed with larger datasets.

Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts

“…S1). This is in agreement with previous studies, reporting on the expression of PTN in mouse embryos at sites of mesenchymal-epithelial Journal of Cell Science 118 (9) interactions (Mitsiadis et al, 1995) and in post-burn hypertrophic scar tissue in humans (Paddock et al, 2003). Keratinocytes might bind PTN via N-syndecan (Syndecan-3), which, in addition to the brain-specific anaplastic lymphoma kinase (ALK) and the protein tyrosine phosphatase ζ (PTP ζ), has been identified as functional PTN receptor (Kinnunen et al, 1998;Maeda and Noda, 1998;Stoica et al, 2001).…”

Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix

“…Thrombospondin-4 is expressed by vascular cells and influences the vessel wall by modulating the proliferation of endothelial cells and smooth muscle cells (35). Recently, an elevated level of expression of thrombospondin-4 has been reported in scar tissue (21). Our results provide the first evidence demonstrating elevated expression of thrombospondin-4 in the late inflammatory phase.…”

Myhre syndrome in a female with previously undescribed symptoms: Further delineation of the phenotype

“…The lack of skin elasticity may be due to defects in collagen or elastic fibrils (or in associated molecules) that do not lead to microscopically visible structural abnormalities but do result in abnormal mechanical behavior. Disturbed organization and metabolism of collagen might also explain the presence of a hypertrophic scar [Paddock et al, 2003].…”