epidermal-growth-factor and Keloid

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

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

Tissue biomechanics regulate a wide range of cellular functions, but the influences on epidermal homeostasis and repair remain unclear. Here, we examined the role of extracellular matrix stiffness on human keratinocyte behavior using elastomeric substrates with defined mechanical properties. Increased matrix stiffness beyond normal physiologic levels promoted keratinocyte proliferation but did not alter the ability to self-renew or terminally differentiate. Activation of epidermal growth factor (EGF) signaling mediated the proliferative response to matrix stiffness and depended on focal adhesion assembly and cytoskeletal tension. Comparison of normal skin with keloid scar tissue further revealed an upregulation of EGF signaling within the epidermis of stiffened scar tissue. We conclude that matrix stiffness regulates keratinocyte proliferation independently of changes in cell fate and is mediated by EGF signaling. These findings provide mechanistic insights into how keratinocytes sense and respond to their mechanical environment, and suggest that matrix biomechanics may play a role in the pathogenesis keloid scar formation.

Topics: Biomechanical Phenomena; Cell Proliferation; Epidermal Growth Factor; Epidermis; Extracellular Matrix; Humans; Keloid; Keratinocytes; Signal Transduction; Skin

Numerous tissue niches in the human body, such as skin, are now recognized to harbour adult stem cells. In this study, we analyze multipotent human dermis-derived progenitor cell populations, isolated and propagated from mechanically and enzymatically processed adult scalp skin. The populations encompass Nestin-positive and -negative cells, which may serve as a convenient and abundant source for various therapeutic applications in regenerative medicine. Here, we show that these cultures exhibit a strong tendency to differentiate into mesodermal derivatives, particularly myofibroblasts, when maintained in media containing serum. Since undesired and excessive myofibroblast formation is a frequent postsurgical complication, we sought culture conditions that would prevent myofibroblast formation. In particular, we analyzed the effect of growth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor AB (PDGF AB). Our results demonstrate that bFGF is a potent inhibitor of mesodermal differentiation, whereas PDFG AB favours myofibroblast formation and up-regulates expression of TGFbeta receptors I and II. This interesting discovery may help in the prevention and treatment of tissue fibrosis and in particular in the eradication of hypertrophic and keloid scars.

Topics: Cell Culture Techniques; Cell Differentiation; Cicatrix; Dermis; Epidermal Growth Factor; Fibroblast Growth Factor 2; Humans; Hypertrophy; Immunohistochemistry; Keloid; Platelet-Derived Growth Factor; Regeneration; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Transforming Growth Factor beta

We investigated the effects of several growth factors on [3H]thymidine incorporation and procollagen type I carboxyterminal propeptide (P1CP) production, which reflects type I collagen metabolism, in keloid and normal fibroblasts.. Six fibroblast cell strains, derived from keloid or normal skin, exhibited similar growth responses to platelet-derived growth factor, transforming growth factor beta 1 (TGF-beta 1), gamma-interferon (gamma-IFN) and histamine. In contrast, keloid fibroblasts showed significantly greater growth response to epidermal growth factor (EGF) than normal fibroblasts. P1CP production was 4.4 times higher in 6 strains of keloid fibroblasts than in 6 controls. Treatment with gamma-IFN (100 U/ml) decreased P1CP production in both groups; the effect was significantly greater in keloid fibroblasts. TGF-beta 1 treatment upregulated P1CP production in both groups. Treatment with histamine increased P1CP production in keloid fibroblasts, although it did not change that in the controls.. EGF and histamine may play some role in the development of keloids.

Topics: Cell Division; Cells, Cultured; Collagen; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Fibroblasts; Growth Substances; Histamine; Humans; Interferon-gamma; Keloid; Male; Peptide Fragments; Platelet-Derived Growth Factor; Procollagen; Recombinant Proteins; Transforming Growth Factor beta

Despite a number of studies, the etiology of keloids remains unknown. We have investigated the response of fibroblasts derived from keloid tissue and normal adult skin to platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF). Keloid fibroblasts were more responsive in both chemotactic and mitogenic assays to all three isoforms of PDGF than fibroblasts from normal skin. No enhanced response of the cells to either EGF or FGF was detected. The enhanced PDGF response of keloid fibroblasts appears to be mediated by elevated levels of PDGF alpha receptors, which are 4-5 times higher than those in normal human skin fibroblasts.

Topics: Adolescent; Adult; Blotting, Western; Chemotaxis; DNA; Epidermal Growth Factor; Female; Fibroblast Growth Factors; Fibroblasts; Humans; Keloid; Male; Middle Aged; Platelet-Derived Growth Factor; Receptors, Platelet-Derived Growth Factor

Keloid fibroblasts were propagated in culture and their proliferative behaviour and response to the Epidermal Growth Factor (EGF) were studied. Keloid fibroblasts grew at a rate which was approximately one-half that of normal age, sex and race matched control fibroblasts. Keloid fibroblasts were stimulated to grow in the presence of EGF (10 ng/ml), but to a lesser degree than the normal control fibroblasts. Scatchard analysis of the binding data obtained using 125I-labeled EGF revealed no difference in binding affinity or receptor numbers between keloid and normal fibroblasts.

Topics: Adult; Cell Division; Cells, Cultured; Epidermal Growth Factor; Fibroblasts; Humans; Keloid; Skin; Time Factors