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Introduction: Cutaneous wounds that involve loss of tissue heal through a complex process of generating granulation tissue to initially cover the wound, followed by epithelialization, and contraction. Normal healing requires a delicate balance between cellular, matrix, and vascularity build up and breakdown. Defects in the regulation of this balance can alter normal scar formation through fibroblastic hyperproliferation, which is characteristic of hypertrophic scar formation., Methods: Primary fibroblasts cultures from hypertrophic scar or adjacent normal skin were seeded in growth medium. Half of each was stimulated with interleukin (IL)-1beta for 6 h and half served as control nonstimulated fibroblasts. Supernatants were tested for expressed proteins and the fibroblasts for changes in gene expression., Results: Comparison between normal skin and hypertrophic scar fibroblasts stimulated with IL-1beta indicate that 15 genes increased and 8 genes decreased expression. When normal skin was stimulated with IL-1beta, there were increases in the expression of heat shock transcription factor-1, hsp70, and IL-6 When hypertrophic scar was stimulated with IL-1beta, there was a decrease in nuclear factor-kappaB, GADD45-alpha, p53, p53 binding protein, and Cox-2 genes. These genes may play specific but different roles in controlling the cellular response to cell stress and apoptosis., Conclusion: Data presented suggest that oxidative and heat stress proteins, stimulated through IL-1beta, may be important mediators of abnormal scarring.

The structural rearrangement of collagen fibres in hypertrophic scar causes abnormal contracture, low tensile strength, and raised scars, which cause functional impairment and disfigurement. It is hypothesized that changes in the genes of cytokines, extracellular matrix proteins, and proteins regulating programmed cell death are related to hypertrophic scar formation. To test this hypothesis, fibroblasts were cultured from hypertrophic scars and their response to interleukin-6 (IL-6) stimulation was studied by defining their gene expression profiles. Affymetrix gene chip analysis was used to identify up- or down-regulation in the 12 625 genes present in the affymetrix array. RT-PCR and ELISA assays were used to validate microarray expression profiles further. Comparison of gene profiles showed an increase of 12 genes in hypertrophic scar fibroblasts compared with normal skin fibroblasts, while the expression of 14 genes decreased. Thirty-three genes were affected by IL-6 treatment in the hypertrophic scar fibroblasts, while 57 genes were affected in normal skin fibroblasts. Messenger RNA to beta-actin ratios for matrix metalloproteinase-1 (MMP-1) and MMP-3 were increased with IL-6 in normal skin fibroblasts from 2.43 +/- 0.06 to 5.50 +/- 0.45 and from 0.75 +/- 0.09 to 1.98 +/- 0.01, respectively. No change in these matrix metalloproteinases could be shown with IL-6 stimulation in hypertrophic scar fibroblasts. Secreted protein levels of pro-MMP-1 and MMP-3 were elevated in the supernatants from normal skin fibroblasts from 2.00 +/- 0.09 and 1.72 +/- 0.10 ng/ml to 4.60 +/- 0.12 and 3.41 +/- 0.20 ng/ml, respectively, after treatment with IL-6 (p < 0.05). No changes were observed in hypertrophic scar fibroblasts treated with IL-6. Values are means +/- SEM. The absence of any up-regulation of MMP-1 and MMP-3 in hypertrophic scar fibroblasts, in response to IL-6, suggests that suppression of matrix metalloproteinases may play a role in the excessive accumulation of collagen formed in hypertrophic scars. While the pathogenesis of abnormal hypertrophic scars remains poorly understood, the use of gene expression arrays may prove helpful in identifying the mechanisms responsible for this type of abnormal scar formation and in formulating an effective therapeutic protocol., (Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Burn injury, it was hypothesized, may induce changes in resistin expression that contribute to postburn metabolic derangements. This study examined resistin gene expression, serum levels of resistin protein, and glucose levels in burned mice., Methods: Ten male Balb-c mice were anesthetized and then given a 30% total burn surface area using heated probes. Burned and sham-burned mice were killed at 2, 4, 24, and 48 hours. The total ribonucleic acid from gonadal fat tissues was isolated for the measurement of resistin gene expression using real-time reverse transcriptase-polymerase chain reaction. Serum levels of resistin, insulin, and glucose were measured. Statistical analysis was performed by two-way analysis of variance using Bonferroni's test to find differences between groups. All p values less than 0.05 were considered significant., Results: Increases in resistin gene expression and serum resistin levels were detected in the burned animals, and these correlated with relative insulin resistance., Conclusion: The findings suggest a potential role for resistin in the pathophysiology of the metabolic response to injury.

Propranolol, a nonselective beta-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 +/- 1.1 yr) were randomized into groups to receive placebo (n = 23) or propranolol (n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 +/- 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was -14.3 +/- 12.9 nmol. min-1. 100 ml leg volume-1 for placebo and +69.3 +/- 34.9 nmol. min-1. 100 ml leg volume-1 in the propranolol-treated children (P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.