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. (1/85)

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.  (+info)

Expression and role of IL-15 in post-burn hypertrophic scars. (2/85)

Hypertrophic scarring is a skin disorder that occurs after wounding and thermal injury. There is accumulating evidence that immunologic processes such as infiltration of activated T lymphocytes and altered cytokine production may play a role in the formation of hypertrophic scars. Interleukin-15, a cytokine identified as a T cell growth factor, also acts as a chemoattractant for T cells and has pro-inflammatory properties. We investigated the expression and the role of this cytokine in hypertrophic scarring. IL-15 expression was compared in skin biopsies of hypertrophic scars (HS) both in active (AHS) and in remission (RHS) phases, in normotrophic scars (NTS) and in normal skin using reverse transcriptase-polymerase chain reaction and immunohistochemistry. IL-15 expression in HS was significantly higher than in NTS or normal skin. Furthermore, AHS expressed higher levels of IL-15 than RHS. Immunohistologic analysis of AHS samples showed strong IL-15 immunoreactivity in keratinocytes and Langerhans cells in the epidermis and in macrophages, fibroblasts, and dermal dendritic cells in the dermis. High levels of IL-15 expression in AHS correlated with abundant infiltration of activated CD3+ cells. Ex vivo experiments indicate that IL-15 can sustain the proliferative response of T cells derived from AHS but not from RHS and NTS. In addition, IL-15 prevents both cytokine deprivation and activation-induced apoptosis of T cells derived from AHS. Taken together, these results suggest that IL-15 can be involved in the recruitment, proliferation, and apoptosis inhibition of T cells in AHS. The findings that the evolution from an AHS to a RHS is associated with a decrease in IL15 expression, and with a loss of IL-15 responsiveness in ex vivo-cultured T cells, indicate that this cytokine plays an important role in the biology of pathologic scar formation.  (+info)

Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars. (3/85)

Reparative process of second and third degree burns usually results in hypertrophic scar formation that can be treated by pressure. Although this method is efficient, its mechanisms of action are not known. In this work, we have studied the histological organization of hypertrophic scars submitted to pressure. Skin biopsies were performed 2 to 7 months after the onset of treatment in two adjacent regions of the scar, non-pressure- or pressure-treated and analyzed by immunohistochemistry and transmission electron microscopy for extracellular matrix organization and cellular morphology. In non-pressure-treated regions, fibrillin deposits did not present the classical candelabra-like pattern under epidermis and were reduced in dermis; in pressure-treated regions the amount was increased compared to non-pressure-treated regions but the organization was still disturbed. In non-pressure-treated regions, elastin was present in patch deposits; in pressure-treated regions elastin formed fibers, smaller than in normal dermis. Tenascin was present in the whole dermis in non-pressure-treated regions, whereas in pressure-treated regions it was observed only under epidermis and around vessels, as in normal skin. alpha-Smooth muscle actin-expressing myofibroblasts were absent in normal skin, present in large amounts in non-pressure-treated regions, and almost absent in pressure-treated regions. The disturbed ultrastructural organization of dermal-epidermal junction observed in non-pressure-treated regions disappeared after pressure therapy; typical features of apoptosis in fibroblastic cells and morphological aspects of collagen degradation were observed in pressure-treated regions. Our results show that, in hypertrophic scars, pressure therapy restores in part the extracellular matrix organization observed in normal scar and induces the disappearance of alpha-smooth muscle actin-expressing myofibroblasts, probably by apoptosis. We suggest that the pressure acts by accelerating the remission phase of the postburn reparative process.  (+info)

Severe obstructive sleep apnoea secondary to pressure garments used in the treatment of hypertrophic burn scars. (4/85)

Obstructive sleep apnoea (OSA) secondary to pressure garments used to treat hypertrophic scarring of burns has never been reported. The present study describes two children who presented with OSA following introduction of such garments for management of hypertrophic scars following severe facial and upper body burns. Complex sleep polysomnography confirmed severe OSA with desaturations sufficient to result in physiological dysfunction that significantly improved on removal of the garments. As there is little evidence to suggest that the use of such garments alters the end result, the potentially serious side effect of obstructive sleep apnoea should be considered before their use is advised.  (+info)

Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor. (5/85)

OBJECTIVE: To explore the characteristics of oncoprotein expression of c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor (bFGF). METHODS: Tissues of hypertrophic scars (n = 8), chronic dermal ulcers (n = 8) and normal skin (n = 5) were taken from 21 patients with burns and chronic dermal ulcers in operation. The ABC immunohistochemical method was used to characterize the gene product expression of c-fos, c-jun and bFGF in the above tissues. RESULTS: In normal skin, both c-fos and c-jun protein expression and bFGF protein expression were observed. The signals of both oncoproteins were localized mainly in subcutaneous fibroblasts, but, positive expression of the bFGF protein was mainly in keratinocytes. In hypertrophic scars, positive expression of both oncoproteins could be found mainly in fibroblasts, but bFGF was mainly in fibroblasts and endothelial cells. In chronic dermal ulcers, endothelial cells, some of inflammatory cells and fibroblasts were positive for both of oncoproteins, but the expression of bFGF was only seen in fibroblasts and endothelial cells. CONCLUSIONS: The results indicate that the interaction between both oncoproteins and bFGF exists, and the regulating action between protooncogenes and bFGF is a major course in wound healing. The different expressions of c-fos and c-jun gene products play an important role in regulate bFGF action, thus affecting wound healing.  (+info)

Alterations in fibroblast alpha1beta1 integrin collagen receptor expression in keloids and hypertrophic scars. (6/85)

Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by excess collagen. Although extensive research has focused on fibroblasts and collagen turnover in these aberrant scars, little work has been done on the expression of integrins (cell membrane structures that link cells to extracellular matrix) within these lesions. Integrin-mediated regulation of collagen synthesis has previously been observed in explanted fibroblasts from normal and fibrotic dermis, and integrin alpha1 knockout mice maintain increased collagen synthesis consistent with a role for alpha1beta1 in providing negative feedback on collagen synthesis. These findings suggested the need to evaluate integrin roles in keloids and hypertrophic scars. In this study we examined integrin expression in keloids (n = 11), hypertrophic scars (n = 5), radiation ulcers (n = 2), and normal skin specimens (n = 8). We used a novel approach to analysis by isolating dermal fibroblasts directly from tissue (without explant culture) and determining surface integrin expression by flow cytometry. We found that keloids and hypertrophic scars have marked alterations in fibroblast integrin expression and contain several distinct populations of fibroblasts. One of these populations expresses high levels of alpha1 integrin, and the proportion of these cells is higher in keloids (63% +/- 3.6% SEM) and hypertrophic scars (45% +/- 2.7% SEM) than in normal skin tissues (28% +/- 4.7% SEM). The different populations of fibroblasts defined by integrin expression merge, however, when the cells are serially cultured, suggesting that there may be aspects of the dermal microenvironment that maintain the integrin phenotypic heterogeneity in dermal fibroblasts.  (+info)

Expression of epidermal growth factor receptor and related phosphorylation proteins in hypertrophic scars and normal skin. (7/85)

OBJECTIVE: To study the potential signal pathway involved in pathogenesis of hypertrophic scar formation. METHODS: The samples of scar were obtained from patients with burn wound scars 6 - 28 months post-burn, while the samples of normal control skin came from the donor site of the same patients. Immunohistochemistry and light microscopy techniques were used to identify the expression of epidermal growth factor receptor (EGFR) and phosphotyrosine proteins (p-Tyr), as well as the phosphorylation of signal transducer and activator of transcription 3 (Stat3) in both hypertrophic scars (n = 6) and normal skin (n = 6). RESULTS: Significant differences were observed in the p-Tyr and EGFR positive expression keratinocytes both in hypertrophic scars and normal skin. The expression of p-Tyr, EGFR and Stat3 protein was greater in hypertrophic scars than in normal skin. However, there was no significant difference in p-Stat3 expression between scar tissues and normal skin. CONCLUSION: Different tyrosine kinase activity occurs in hypertrophic scars and normal cutaneous tissues. Initially, varied expression of EGFR is due to different ligand stimulations. However, phosphotyrosine protein and Stat3 are subsequently activated through phosphorylation. In scar tissues, although EGFR has an intrinsic tyrosine kinase activity when activated by EGFR correlated ligand, phosphorylation of Stat3 showed no significant changes. Therefore, cellular signal pathways are induced by EGFR, which might play a role in hypertrophic scar pathogenesis.  (+info)

Prevention and treatment of excessive dermal scarring. (8/85)

Today, wound management to avoid excessive scar formation is increasingly important, especially in populations with Fitzpatrick 3 or higher skin pigmentation. Medical science and industrial development are devoting more effort toward understanding and offering better therapy to control scars. However, advances in scar management have been hampered by the confusing or ambiguous terminology. There is no consensus on what amount of post-traumatic skin scar formation is "normal" and what should be considered "hypertrophic". In the World Health Organization's ICD-9, there is no diagnostic code for hypertrophic scar--only keloid is listed. Yet, the medical and scientific literature distinguishes them as different conditions. Our experience suggests that the diagnosis of keloid disease is greatly over-rendered. For black patients, an elevated scar seems, by default, diagnosed as keloid by most. This confusion results in inappropriate management of scar formation, and occasionally contributes to decision making related to elective or cosmetic surgery. Given that patients are expecting better outcomes from wound care today than in the past, this review article attempts to capture the essential biological factors related to wound scar production and discusses treatment options and indications used by the authors.  (+info)

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