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Gene expression profiles from hypertrophic scar fibroblasts before and after IL-6 stimulation.
- Source :
-
The Journal of pathology [J Pathol] 2004 Apr; Vol. 202 (4), pp. 476-85. - Publication Year :
- 2004
-
Abstract
- 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.<br /> (Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
- Subjects :
- Cells, Cultured
Child
Child, Preschool
Cicatrix, Hypertrophic pathology
Enzyme-Linked Immunosorbent Assay
Female
Fibroblasts drug effects
Gene Expression Profiling
Humans
Male
Matrix Metalloproteinase 1 biosynthesis
Matrix Metalloproteinase 1 genetics
Matrix Metalloproteinase 3 biosynthesis
Matrix Metalloproteinase 3 genetics
Reverse Transcriptase Polymerase Chain Reaction
Skin cytology
Skin metabolism
Cicatrix, Hypertrophic metabolism
Fibroblasts metabolism
Gene Expression Regulation drug effects
Interleukin-6 pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3417
- Volume :
- 202
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 15095275
- Full Text :
- https://doi.org/10.1002/path.1539