epidermal-growth-factor and Cicatrix--Hypertrophic

Growth factors are becoming extremely valuable tools in our attempts to understand the mechanisms that modulate cellular activities. Their targeting to appropriate cells and maintaining adequate pharmacological levels becomes essential, particularly in view of the different effects that these compounds have on various cells and the dose dependence of their response. Within this context, this review focuses primarily on the delivery of growth factors involved in the processes of wound healing and tissue repair.

Topics: Animals; Biocompatible Materials; Biomedical Engineering; Bone Morphogenetic Proteins; Cicatrix, Hypertrophic; Drug Delivery Systems; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fracture Healing; Growth Substances; Humans; Keloid; Nerve Growth Factors; Peptides; Platelet-Derived Growth Factor; Transforming Growth Factor beta; Wound Healing

Treatment of hypertrophic scars can be difficult for both patients and physicians. Silicone-containing gel dressings have been reported to be an effective alternative treatment for hypertrophic scars, yet the mechanism of action of these dressings is unknown.. To determine whether silicone is an essential factor in the treatment of hypertrophic scars and investigate the effects of occlusive dressing therapy on the expression of key wound healing mediators.. A pilot paired comparison, nonrandomized study was conducted comparing a silicone gel sheeting (Silastic [SGS]) with a hydrogel dressing (ClearSite). The effects of the dressings were compared side by side in the treatment of 15 hypertrophic scars at both the clinical and molecular levels through the use of reverse transcriptase/polymerase chain reaction to evaluate effects on the expression of interleukin 8 (IL-8), basic fibroblast growth factor (bFGF), granulocyte-macrophage colony-stimulating factor (GMCSF), epidermal growth factor (EGF), transforming growth factor beta (TGF-beta), and fibronectin.. Comparable clinical improvement of the hypertrophic scars was obtained with both dressings. Treatment of hypertrophic scars resulted in increased mean levels of IL-8, bFGF, and GMCSF mRNA; while mean TGF beta and fibronectin mRNAs decreased after treatment with both dressings. Comparison between the two dressings revealed significant changes in IL-8 and fibronectin mRNA levels after treatment with ClearSite, while only fibronectin changes were significant after treatment with SGS with respect to normal skin. Only ClearSite induced significant changes in IL-8 and bFGF levels when untreated scars were compared with posttreatment lesions, suggesting that the hydrogel augments collagenolysis via promotion of inflammation.. This study demonstrates that silicone is not a necessary component of occlusive dressings in the treatment of hypertrophic scars. The pathogenesis of hypertrophic scars is further elucidated by demonstrating that there is molecular evidence for extensive connective tissue remodeling occurring during occlusive dressing therapy.

Topics: Adult; Aged; Cicatrix, Hypertrophic; Collagen; Connective Tissue; Cytokines; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fibronectins; Gels; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Interleukin-8; Middle Aged; Occlusive Dressings; Pilot Projects; Polyethylene Glycols; Polymerase Chain Reaction; Polyurethanes; RNA, Messenger; Silicone Elastomers; Silicones; Skin; Transforming Growth Factor beta; Wound Healing

Keloid and hypertrophic scars are skin fibrosis-associated disorders that exhibit an uncontrollable proliferation of fibroblasts and their subsequent contribution to the excessive accumulation of extracellular matrix (ECM) in the dermis. In this study, to elucidate the underlying mechanisms, we investigated the pivotal roles of epidermal growth factor (EGF) in modulating fibrotic phenotypes of keloid and hypertrophic dermal fibroblasts. Our initial findings revealed the molecular signatures of keloid dermal fibroblasts and showed the highest degree of skin fibrosis markers, ECM remodeling, anabolic collagen-cross-linking enzymes, such as lysyl oxidase (LOX) and four LOX-like family enzymes, migration ability, and cell-matrix traction force, at cell-matrix interfaces. Furthermore, we observed significant EGF-mediated downregulation of anabolic collagen-cross-linking enzymes, resulting in amelioration of fibrotic phenotypes and a decrease in cell motility measured according to the cell-matrix traction force. These findings offer insight into the important roles of EGF-mediated cell-matrix interactions at the cell-matrix interface, as well as ECM remodeling. Furthermore, the results suggest their contribution to the reduction of fibrotic phenotypes in keloid dermal fibroblasts, which could lead to the development of therapeutic modalities to prevent or reduce scar tissue formation.

Topics: Adult; Cell Movement; Cells, Cultured; Cicatrix, Hypertrophic; Elastic Modulus; Enzymes; Epidermal Growth Factor; Extracellular Matrix; Female; Fibroblasts; Fibrosis; Humans; Hydrogels; Keloid; Male; Middle Aged; Skin

To investigate the mechanism of overhealing alleviation by salvia miltiorrhiza (SM) in wound healing.. Fibroblasts were cultured in vitro, and SM was applied with different concentrations (40, 80, 160 and 320 micrograms/ml) and time(the 1st, 2nd, 3rd, 4th and 5th days) to influence their autocrine. The levels of transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) were determined by ELIAS and radioimmunoassay respectively.. The SM could inhibit autocrine of TGF-beta 1 by fibroblasts (P < 0.05). However, it did not affect autocrine of EGF (P > 0.05).. The above results indicate that SM reduces overhealing by inhibiting the autocrine of TGF-beta 1 selectively.

Topics: Cell Division; Cells, Cultured; Child; Cicatrix, Hypertrophic; Collagen; Drugs, Chinese Herbal; Epidermal Growth Factor; Extracellular Matrix; Fibroblasts; Humans; Salvia miltiorrhiza; Time Factors; Transforming Growth Factors; Wound Healing

We have examined the effects of four 'exogenous' growth factors, i.e. PDGF-BB (5 ng/ml), TGF-beta1 (5 ng/ml), bFGF (10 ng/ml) and EGF (10 ng/ml) on the contraction of floating collagen type I lattices populated by human normal skin (NS) and hypertrophic scar (HS) fibroblasts (FPCL). Only TGF-beta1 enhanced the contractility of both NS and HS fibroblasts in the collagen lattice (P < 0.01). Other growth factors (PDGF-BB, bFGF and EGF) did not affect FPCLs contraction at 72 h (P > 0.05). The onset effect of TGF-beta1 on NS-FPCL contraction was relative early at 24 h after FPCL casting as compared to a 72 h delay on HS-FPCL contraction. Besides, PDGF-BB was found to be able to enhance HS-FPCL contraction (P < 0.05) but not on NS-FPCL contraction on day 4. On the other hand, three enzyme-linked immunosorbent assays (ELISA) were performed to demonstrate quantitatively the 'endogenous' growth factors that fibroblasts secreted into the culture medium 48 h after FPCL casting. No appreciable difference was found between 10 NS and 11 HS samples tested for PDGF-AB immunoassay (11.48 +/- 5.5 pg/ml versus 12.20 +/- 5.34 pg/ml). The same result existed in 7 NS and 13 HS samples for TGF-beta2 immunoassay (15.15 +/- 6.2 pg/ml versus 11.84 +/- 7.46 pg/ml). In bFGF immunoassay study, relative variable data was noted in both 7 NS (18.18 +/- 13.18 pg/ml) and 12 HS samples (20.41 +/- 22.36 pg/ml). In conclusion, we suppose that TGF-beta role in wound healing may be due to the secondary exogenous influences. The endogenous ability of TGF-beta2 secretion (quantity) in HS fibroblasts are the same as NS fibroblasts but with delayed timing responses (quality) to exogenous TGF-beta1 effect in the collagen lattice. Further studies with timing-regulated selective specific monoclonal antibodies against the growth factor receptors may provide the therapeutic applications on HS during wound healing.

Topics: Becaplermin; Cells, Cultured; Cicatrix, Hypertrophic; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fibroblasts; Growth Substances; Humans; Platelet-Derived Growth Factor; Proto-Oncogene Proteins c-sis; Receptors, Growth Factor; Skin; Transforming Growth Factor beta; Wound Healing

The alteration of normal dermal fibroblast function that leads to the development of hypertrophic scar after thermal injury is unknown. To determine functional differences that might explain this process, fibroblasts were cultured from biopsies of post-thermal injury mature hypertrophic scars and patient-matched normal skin. The mitogenic responses of scar cells to fetal bovine serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor necrosis factor alpha (TNF alpha) were determined and compared to normal skin cells. Collagen synthetic rate was also compared in the presence and absence of transforming growth factor beta 1 (TGF beta 1). Whereas both scar and normal cells responded with increased thymidine uptake to serum and cytokines, the stimulation to EGF and serum was significantly lower in scar cells. In contrast, synthesis of collagen, but not of non-collagenous proteins, was increased in scar relative to normal cells, both basally and when stimulated with low doses of TGF beta 1. Additionally, the fraction of protein synthesized as collagen was significantly higher in scar fibroblasts. These results suggest that fibroblasts from hypertrophic scars demonstrate stable phenotypic differences in cytokine responsiveness in comparison to cells from unaffected skin. The increased rate of collagen synthesis and decreased responsiveness to mitogens are consistent with the increased extracellular matrix content and decreased cellularity of hypertrophic scars.

Topics: Adolescent; Adult; Aged; Child; Cicatrix, Hypertrophic; Collagen; Cytokines; Epidermal Growth Factor; Female; Fibroblasts; Humans; Male; Middle Aged; Mitogens; Phenotype; Platelet-Derived Growth Factor; Skin; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha