epidermal-growth-factor and Cicatrix

Glial cells in the central nervous system of adult mammals outnumber neurons 10-fold. Their number remains stationary throughout adulthood, controlled by the concomitant presence of mitogens and mitogen inhibitors. The most abundant inhibitor, neurostatin, is ganglioside GD1b O-acetylated on hydroxyl 9 of its outermost sialic acid. Neurostatin inhibited the proliferation of primary microglia and astroblasts in culture (cytostatic) as well as both rodent and human glioma cells (cytotoxic) at nanomolar concentrations. At those concentrations neurostatin had no effect on non-glial lineage cells or differentiated glia. Neurostatin shows direct antimitotic activity on tumoral cells, interfering with multiple signals regulating cell cycle progression. But it also promotes indirectly total destruction of experimental rat brain glioma, presumably by making it visible to the host immune system and activating CD4+ and CD8+ lymphocytes. Neurostatin could be a new anti-inflammatory agent, with multiple convergent direct and indirect actions on glioma growth, a pathology without satisfactory clinical treatment. Neurostatin is produced by neurons but its expression is up-regulated by neuron-astrocyte contact. The action of neurostatin could be mediated by a number of receptor proteins, including integrins, Toll-like receptors and siglecs.. Glicolipidos neuronales regulan negativamente la division glial durante el desarrollo y tras una lesion.. En el sistema nervioso central de los mamiferos, las celulas gliales superan diez veces en numero a las neuronas. Su numero permanente estacionario durante la edad adulta, controlado por la presencia simultanea de mitogenos gliales e inhibidores de esos mitogenos. El inhibidor mas abundante, la neurostatina, es el gangliosido GD1b O-acetilado en el grupo 9 del acido sialico mas externo. La neurostatina y los oligosacaridos sinteticos inhiben la proliferacion de astroblastos en cultivo primario (citostaticos) y de celulas de gliomas (citotoxicos), tanto de roedores como de humanos, en concentracion nanomolar. A esas concentraciones, la neurostatina no tuvo efecto sobre celulas de linaje no glial ni sobre glia madura. La neurostatina y sus analogos mostraron actividad antimitotica directa sobre las celulas tumorales, interfiriendo con la progresion del ciclo celular en multiples sitios, pero tambien actuaron indirectamente, haciendo visibles las celulas tumorales al sistema inmune del huesped y activando linfocitos CD4+ y CD8+. Analogos de neurostatina podrian generar nuevos farmacos antiinflamatorios, con multiples acciones directas e indirectas contra el crecimiento de gliomas, una patologia todavia sin tratamiento clinico satisfactorio. La neurostatina es producida por las neuronas, pero el contacto de estas con astrocitos estimula notablemente su expresion. La accion de la neurostatina puede estar mediada por numerosas proteinas receptoras, incluyendo integrinas, siglecs y receptores Toll-like.

Topics: Animals; Brain Injuries; Carbohydrate Conformation; Carbohydrate Sequence; Cell Division; Cicatrix; Epidermal Growth Factor; Gangliosides; Glioma; Glycolipids; Glycosphingolipids; Humans; Integrins; Intercellular Signaling Peptides and Proteins; Macrophages; Mammals; Mice; Neural Stem Cells; Neurogenesis; Neuroglia; Neurons; Spinal Cord Injuries; Toll-Like Receptors; Xenograft Model Antitumor Assays

Topics: Animals; Cicatrix; Epidermal Growth Factor; Fibroblast Growth Factors; Humans; Surgery, Plastic; Transforming Growth Factor beta; Wound Healing

The healing of an adult skin lesion is a well studied but complex affair of some considerable clinical interest. Endogenous growth factors, including the EGF, FGF, PDGF and TGF beta families, are released at the wound site and presumed to be a necessary part of the natural wound healing machinery. Moreover, members of each of these families have been shown to enhance healing if added exogenously to a wound site. In this review we shall briefly discuss what is known about the mechanics and cell biology of adult wound healing, describe the normal cellular source of growth factors during the healing process and, with reference to their known capacities in tissue culture, speculate as to how particular growth factors might be able to enhance healing.

Topics: Animals; Cells, Cultured; Cicatrix; Connective Tissue; Epidermal Growth Factor; Fibrin; Fibroblast Growth Factors; Gene Expression Regulation; Growth Substances; Humans; Inflammation; Keratinocytes; Male; Mice; Platelet-Derived Growth Factor; Receptors, Cell Surface; Salivary Proteins and Peptides; Skin; Transforming Growth Factors; Wound Healing

Cesarean section (CS) is a major surgical intervention that affects women at childbearing age. Scarring from CS potentially causes discomfort and psychological distress. Emerging evidence indicates that epidermal growth factor (EGF) plays crucial roles in wound healing with the potential of minimizing scar formation. This study aims to investigate the effect of microencapsulated recombinant human EGF (Me-EGF) in scar prevention. Silicone gel was incorporated as part of the routine scar treatment.. Healthy women scheduled for cesarean delivery were enrolled and randomized to three groups: (1) no scar treatment, (2) silicone gel only, or (3) silicone gel plus Me-EGF. Vancouver Scar Scale (VSS: vascularity, pigmentation, elasticity, and height) was used for scar assessment at the 6th month and 9th month after CS.. A total of 60 women were enrolled, but one patient withdrew due to noncompliance with the follow-up visit requirement. Me-EGF-containing treatment group consistently scored the lowest on every parameter in the VSS scale, followed by silicone gel group, and the group with no scar treatment. Kruskal-Wallis tests indicated significant differences (p < 0.05) between Me-EGF-containing treatment group and the other two groups in vascularity, pigmentation, elasticity, and the VSS total score, at either 6th month, 9th month, or both time points. The only parameter not showing any significant between-group difference was scar height, but the pattern still remained the same, in which Me-EGF group scored better in both month 6 and 9.. Surgical incisions in lower abdomen posed challenge in scar management. Our findings suggest that Me-EGF is a potential therapeutic option for better wound healing and scar prevention.

Topics: Adult; Cesarean Section; Cicatrix; Drug Compounding; Epidermal Growth Factor; Female; Gels; Humans; Pregnancy; Surgical Wound; Treatment Outcome; Wound Healing

BACKGROUND: Atrophic scarring in skin of color is a common, permanent, and distressing result of uncontrolled acne vulgaris. Ablative lasers and chemical peels are frequently used to improve the appearance of atrophic scars, primarily through the stimulation of collagen and elastin; however, these treatment modalities are associated with risks, such as dyspigmentation and hypertrophic scarring, especially in patients with darker skin.

OBJECTIVE: We evaluated the efficacy of topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars in skin of color.

METHODS: A single-center clinical trial was performed on twelve healthy men and women (average age 32.5) with Fitzpatrick Type IV-V skin and evidence of facial grade II-IV atrophic acne scars. Subjects applied topical EGF serum to the full-face twice daily for 12 weeks. Scar improvement was investigated at each visit using an Investigator Global Assessment (IGA), a Goodman grade, clinical photography, and patient self-assessment.

RESULTS: Eleven subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 3.36 (SEM = 0.15) to 2.18 (SEM = 0.33). Mean Goodman grade was reduced from 2.73 (SEM = 0.19) to 2.55 (SEM = 0.21). Of the eleven pairs of before and after photographs, nine were correctly chosen as the post-treatment image by a blind investigator. On self-assessment, 81% reported a "good" to "excellent" improvement in their scars compared to baseline (P = 0.004).

CONCLUSION: Topical EGF may improve the appearance of atrophic acne scars in skin of color. Additional, larger studies should be conducted to better characterize improvement.

J Drugs Dermatol. 2017;16(4):322-326.

Topics: Acne Vulgaris; Administration, Cutaneous; Adolescent; Adult; Atrophy; Cicatrix; Epidermal Growth Factor; Face; Female; Humans; Male; Middle Aged; Pilot Projects; Quality of Life; Self-Assessment; Skin; Skin Pigmentation; Treatment Outcome; Young Adult

Atrophic acne scars are a common and psychologically devastating sequela of acne vulgaris that are refractory to the vast majority of topical treatments.. We evaluated the efficacy of a topically applied synthetic epidermal growth factor (EGF) serum in reducing the appearance of atrophic acne scars.. A single-center clinical trial was performed on nine self-selected male and female patients with Goodman & Baron grade II-IV atrophic acne scars. Subjects followed a standardized treatment regimen, including twice-daily application of EGF serum to scarred areas over 12 weeks. Subject progress was evaluated at baseline and 4-week intervals by clinical photography, Investigator Global Assessment (IGA), Goodman grade and patient self-assessment. Final patient perceptions were shared by written self-assessment at the end of the study. Before and after photographs were also evaluated by a blind investigator.. Eight subjects completed the trial. Compared to baseline, there was an improvement in mean IGA score from 2.875 (SEM= .327) to 2.38 (SEM = .375). Mean Goodman grade was reduced from 3.00 (SEM = .309) to 2.75 (SEM = .25). Of the eight pairs of before and after photographs given to a blind investigator, five were correctly chosen as the post-treatment image. Two were assessed as "excellent" (76-100%) improvement and three were assessed as "good" (50-75%) improvement. A one-tailed paired student t-test (α = .05) using blind investigator ratings of scar severity for each before and after photograph yielded a P-value of .0019, confirming the difference as statistically significant. On final self-assessment, all but one patient reported "good" to "excellent" improvement in their scars compared to baseline. 75% of patients who received alternative treatments in prior years reported EGF serum to be more efficacious.. These results suggest that topical EGF may improve the appearance of atrophic acne scars, though further study and more objective evaluation measures are required for definitive conclusions to be drawn.

Topics: Acne Vulgaris; Administration, Topical; Adult; Atrophy; Cicatrix; Epidermal Growth Factor; Facial Dermatoses; Female; Humans; Male; Middle Aged; Photography; Pilot Projects; Severity of Illness Index; Single-Blind Method; Treatment Outcome; Young Adult

Topics: Animals; Cicatrix; Epidermal Growth Factor; Hyperplasia; Male; Rabbits; Stem Cells; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A; Wound Healing

The inflammatory lesions of acne leave scars which greatly affect patients' quality of life. Treatment options targeting both acne and acne scars are still lacking.. To evaluate the clinical efficacy of epidermal growth factor ointment (EGFO) on acne and acne scars.. The study design was 12-week, prospective, split-face, single-blinded. The 36 patients with mild to moderate acne vulgaris applied EGFO on one side of the face and the vehicle ointment on the other side twice daily. The patients were assessed every 4 weeks by acne lesion and scar counts, investigator's global assessment for acne (IGA) and scar (SGA), and the ECCA scar grading scale. Biopsies were performed before and after treatment.. Acne and acne scars were significantly improved on EGFO-treated sides, while control sides were not. Acne lesion and scar counts were significantly reduced after 4 weeks, while IGA, SGA, and ECCA grade significantly decreased after 8 weeks. Immunohistochemistry showed decreased expression of keratin 16, NF-κB p65, IL-1α, and IL-8, and increased expression of TGF-β1, elastin, and collagen type 1, 3 after treatment.. EGFO can be a treatment option targeting acne and acne scars.

Topics: Acne Vulgaris; Cicatrix; Epidermal Growth Factor; Humans; Immunoglobulin A; Ointments; Prospective Studies; Quality of Life; Treatment Outcome

Scars are common and intractable consequences after scalded wound healing, while monotherapy of epidermal growth factors does not solve this problem. Maintaining the stability of epidermal growth factors and promoting scarless healing of wounds is paramount. In this study, engineering cellular nanovesicles overexpressing PD-L1 proteins, biomimetic nanocarriers with immunosuppressive efficacy, were successfully prepared to encapsulate epidermal growth factors for maintaining its bioactivity. Remarkably, PD-L1 cellular nanovesicles encapsulating epidermal growth factors (EGF@PDL1 NVs) exerted desired therapeutic effect by attenuating the overactivation of T cell immune response and promoting skin cells migration and proliferation. Hence, EGF@PD-L1 NVs promoted wound healing and prevented scarring in deep second-degree scald treatment, demonstrating a better effect than using individual PD-L1 NVs or EGF. This research proved that EGF@PD-L1 NVs is considered an innovative and thorough therapy of deep second-degree scald.

Topics: B7-H1 Antigen; Burns; Cicatrix; Epidermal Growth Factor; Humans; Skin; Wound Healing

Development of advanced wound dressing materials with rapid healing rates is in urgent demand for wound cares. A suitable microenvironment will promote cell proliferation and migration, which benefits to early wound healing and prevents inflammations and scars. In this work, N-carboxymethyl chitosan- and alginate-based hydrogels are prepared via both electrostatic interaction and divalent chelation with epidermal growth factor (EGF) payload to promote the cell proliferation and wound healing. The dual-crosslinked hydrogels are investigated in terms of rheology, water retention ability, and the release rate of EGF. Moreover, such amorphous hydrogel can promote cell proliferation and accelerate wound healing. The present study demonstrates that dual-crosslinked polysaccharide hydrogels are promising in wound care management.

Topics: Alginates; Animals; Bandages; Cell Movement; Cell Proliferation; Cellular Microenvironment; Chitosan; Cicatrix; Cross-Linking Reagents; Epidermal Growth Factor; Humans; Hydrogels; Inflammation; Mice; Polysaccharides; Wound Healing

Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury

Topics: Animals; Astrocytes; Axons; Cicatrix; Electrophysiology; Epidermal Growth Factor; Female; Fibroblast Growth Factors; Glial Cell Line-Derived Neurotrophic Factor; Hydrogels; Laminin; Male; Mice; Mice, Inbred C57BL; Nerve Regeneration; Neuroglia; Proteoglycans; Rats; Rats, Inbred Lew; Recovery of Function; Spinal Cord Injuries; Spinal Cord Regeneration; Stromal Cells

Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing. The NMSF based mats exhibited essential properties of wound dressing like biocompatibility, high water retention capacity (440%), water vapor transmission rate (∼2330gm. A facile fabrication of a ready-to-use bioactive wound dressing capable of concomitantly accelerating the healing process as well as deposition of the extracellular matrix (ECM) to circumvent further scarring complicacies has become a focal point of research. In this backdrop, our present work is based on non-mulberry silk fibroin (NMSF) electrospun antibiotic loaded semi-occlusive mats, mimicking the ECM of skin in terms of morphology, topology, microporous structure and mechanical stiffness. Regulation of ECM deposition and isotropic orientation evinced the potential of the mat as an instructive platform for skin regeneration. The unique peptide motifs of NMSF assisted the augmented recruitment of fibroblast, keratinocytes and endothelial cells leading to accelerated wound healing. Early progression of mature granulation, faster re-epithelialization and angiogenesis in the wounds in in vivo rabbit model forwarded the blended nanofibrous mats of NMSF and PVA ferrying EGF, apt for scarless healing.

Topics: Animals; Anti-Bacterial Agents; Cell Proliferation; Cell Shape; Cell Survival; Cicatrix; Collagen; Drug Liberation; Elastin; Epidermal Growth Factor; Extracellular Matrix; Fibroblasts; Fibroins; Humans; Implants, Experimental; Mice; Microbial Sensitivity Tests; Microscopy, Atomic Force; Morus; Nanofibers; Rabbits; Steam; Subcutaneous Tissue; Wound Healing

Epidermal growth factor (EGF) decreases inflammatory cell infiltration and TGF-β expression during wound healing. Several clinical studies show that recovery of various ulcer wounds, such as diabetic and radiation ulcer, is promoted by EGF.. To evaluate effects of recombinant human epidermal growth factor (rhEGF) on cutaneous scar quality after thyroidectomy.. Scar quality was evaluated by Vancouver scar scale (VSS) in two groups of female thyroidectomy patients (control, n = 11; rhEGF-treated, n = 10). Scar erythema, pigmentation, elasticity and hydration were measured by mexameter, cutometer and corneometer.. Scar pliability (at 4 weeks) and thickness (2 weeks) after surgery were significantly lower in the rhEGF group than control. Total VSS score was significantly lower in the rhEGF group after 4 weeks. However, erythema, pigmentation, elasticity and hydration of the scar were not significantly different between groups.. The early use of rhEGF in surgical wound healing may improve cutaneous scar quality.

Topics: Adult; Cicatrix; Epidermal Growth Factor; Erythema; Female; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Thyroidectomy; Wound Healing

Topics: Animals; Cicatrix; Epidermal Growth Factor; Fibrosis; Humans; Inflammation; Interferon-gamma; Interleukin-10; Ligands; Mice; Models, Biological; Receptors, CXCR3; Signal Transduction; Stress, Mechanical; Wound Healing

A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta(1) in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta(1), and mediating the formation of collagen.

Topics: Animals; Cicatrix; Collagen; Epidermal Growth Factor; Humans; Inflammation; Mice; Recombinant Proteins; Skin; Wound Healing

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

To investigate hepatocyte growth factor (HGF) primed fibroblasts and decorin application on skin and vocal fold fibroblasts in vitro and in vivo in rabbit vocal fold scar model.. Vocal fold and skin fibroblasts underwent five in vitro treatment conditions: control, epidermal growth factor, HGF, both decorin and HGF, and decorin alone. Hyaluronic acid and collagen enzyme-linked immunosorbent assays were performed. In vivo, 12 rabbits underwent unilateral vocal fold stripping. Injured vocal folds were then injected with skin fibroblasts, HGF, HGF-primed fibroblasts and decorin, or decorin. Outcomes included histologic and lamina propria height analyses.. In vitro, HGF increased hyaluronic acid synthesis in vocal fold fibroblasts (P<0.001). HGF and decorin treatment diminished collagen secretion (P<0.01). In vivo, histologic findings indicated minimal difference in collagen amount between treatment groups.. HGF and decorin together may decrease collagen production by skin and vocal fold fibroblasts. Fibroblast transplantation into scarred vocal folds has equivocal benefit.

Topics: Animals; Cells, Cultured; Cicatrix; Collagen Type I; Decorin; Disease Models, Animal; Epidermal Growth Factor; Extracellular Matrix Proteins; Female; Fibroblasts; Hepatocyte Growth Factor; Hyaluronic Acid; Proteoglycans; Rabbits; Skin; Vocal Cords

Beta-catenin is a critical regulator of cell behavior during embryogenesis and neoplastic processes. It also plays a crucial role in repair by modulating dermal fibroblast activity during the proliferative phase of cutaneous wound healing. We hypothesize that growth factors liberated during the initial phase of wound healing convey signals to induce activation of beta-catenin-mediated TCF-dependent signaling during the proliferative phase. Dermal fibroblasts were isolated and cultured from mice containing a beta-galactosidase reporter responsive to beta-catenin-TCF transactivation (TCF-beta-gal). Cells were stimulated with growth factors present at the initial phase of wound healing. EGF and TGF-beta1 significantly increased beta-catenin protein levels and transcriptional activity, whereas beta-catenin mRNA expression was unaffected. This increase was attributed to inactivation of GSK-3beta, a kinase important for beta-catenin destabilization. Subcutaneous injection of EGF or TGF-beta1 before wounding of TCF-beta-gal mice resulted in larger scars and fibroblasts within these wounds that strongly stained for beta-galactosidase, indicating significant beta-catenin transcriptional activity in vivo. Thus, beta-catenin-mediated signaling is activated downstream of growth factors released during the initial phase of wound repair, and may act during the proliferative phase of wound healing to integrate signals from initial phase factors into the expression of genes important during the later, remodeling phase.

Topics: Animals; beta Catenin; beta-Galactosidase; Cell Division; Cells, Cultured; Cicatrix; Cytoskeletal Proteins; Dermis; DNA-Binding Proteins; Epidermal Growth Factor; Fibroblasts; Gene Expression Regulation, Developmental; Genes, Reporter; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Growth Substances; Lymphoid Enhancer-Binding Factor 1; Mice; Mice, Transgenic; RNA, Messenger; Signal Transduction; Trans-Activators; Transcription Factors; Transcriptional Activation; Transforming Growth Factor beta; Transforming Growth Factor beta1; Wound Healing

Epidermal growth factor receptor (EGFR) is expressed in reactive astrocytes following injury in the CNS. However, the effects of activation of the EGFR pathway in astrocytes are not well established. In the present study, we demonstrate that activation of EGFR causes optic nerve astrocytes, as well as brain astrocytes, to form cribriform structures with cavernous spaces. Formation of the cribriform structures is dependent on new protein synthesis and cell proliferation. Platelet-derived growth factor and basic fibroblast growth factor were not effective. Smooth muscle cells and epithelial cells do not form cribriform structures in response to EGFR activation. The formation of the cribriform structures appears to be related to a guided migration of astrocytes and the expression of integrin beta1 and extracellular fibronectin in response to activation of EGFR. The EGFR pathway may be a specific, signal transduction pathway that regulates reactive astrocytes to form cavernous spaces in the glial scars following CNS injury and in the compressed optic nerve in glaucomatous optic nerve neuropathy.

Topics: Adult; Astrocytes; Cell Communication; Cell Division; Cell Movement; Cells, Cultured; Cicatrix; Cytoskeleton; Epidermal Growth Factor; ErbB Receptors; Extracellular Space; Fibronectins; Glaucoma; Humans; Integrin beta1; Middle Aged; Optic Disk

Twenty years ago, surgeons noted the ability of early-gestation fetal skin to heal in a scarless manner. Since that time, numerous investigators have attempted to elucidate the mechanisms behind this phenomenon. As a result of this effort, it is now well established that many animals undergo a transition late in development from scarless cutaneous healing to a scar-forming, adultlike phenotype. The authors have been interested in the role played by cytokines known to be involved in the adult wound-healing process and how they relate to scarless repair. They therefore asked the following question: Are genes for epidermal growth factor (EGF) and platelet-derived growth factor-B (PDGF-B) expressed differentially as a function of gestational age in fetal rat skin and dermal fibroblasts? To answer this question, skin from fetal Sprague-Dawley rats (N = 56) at time points that represented both the scarless and scar-forming periods of rat gestation was harvested. In addition, fibroblasts derived from fetal rat skin were cultured in vitro at similar times. These cells were expanded in culture and, when confluent, total ribonucleic acid from both fibroblasts and whole skin was extracted and subjected to Northern blot analysis with probes for EGF and PDGF-B. Results demonstrated that neither EGF nor PDGF-B gene expression changed markedly as a function of gestational age in fetal fibroblasts alone. In whole skin, however, both EGF and PDGF-B demonstrated a marked decrease in gene expression with increasing gestational age. Furthermore, the most striking decrease in gene expression for both cytokines came between 16 and 18 days of gestation-the transition point between scarless and scar-forming repair in the fetal rat. These data suggest that EGF and PDGF may play a role in the mechanism of scarless cutaneous repair. Moreover, it appears that fetal fibroblasts are not the cell type responsible for this differential gene expression. These results raise questions about the unique cytokine milieu likely to be present during the time of scarless healing and the cells that ultimately guide the mechanisms leading to skin regeneration.

Topics: Animals; Blotting, Northern; Cell Culture Techniques; Cicatrix; Epidermal Growth Factor; Female; Fibroblasts; Gene Expression; Gestational Age; Proto-Oncogene Proteins c-sis; Rats; Rats, Sprague-Dawley; RNA, Messenger; Skin; Wound Healing

In order to shed further light on the potential role of mast cells during tissue turnover, we have investigated the number of mast cells containing only tryptase and those storing both tryptase and chymase by enzyme histochemistry in normal versus healing skin. Furthermore, we have studied the in vitro effect of these enzymes on the mitogenesis of subconfluent quiescent fibroblast and HaCaT keratinocyte cultures, using flowcytometric DNA analysis. Chymase-containing mast cell numbers were markedly decreased in scars (P<0.001), whereas the overall number of tryptase-containing mast cells was not decreased, although these cells were smaller and stained more faintly in scars. Chymase (5 to 300 mU/ml) induced a marked, dose-dependent in vitro mitogenic response in 3T3 fibroblasts, whereas the effects of tryptase, at up to 60 nM, were only moderate, compared to the known fibroblast mitogens EGF, TGF-alpha, alpha-thrombin and trypsin at optimal concentrations. Coincubation of either protease with EGF or alpha-thrombin had additive effects. In contrast to fibroblasts, keratinocytes showed only minor mitogenic responses to tryptase and chymase, also in comparison to other known mitogenic stimuli, and responses to EGF and alpha-thrombin were inhibited on costimulation of cells with the proteases. These findings document for the first time a potential role of mast cell chymase in connective tissue repair, with tryptase being less active on fibroblasts, and with inhibitory effects of both mast cell proteases on keratinocytes.

Topics: 3T3 Cells; Animals; Cell Count; Cell Division; Cell Line; Chymases; Cicatrix; Connective Tissue; Culture Media; Dose-Response Relationship, Drug; Epidermal Growth Factor; Fibroblasts; Humans; Keratinocytes; Mast Cells; Mice; Mitogens; Mitosis; Serine Endopeptidases; Skin; Transforming Growth Factor alpha; Tryptases

To explore the effects of endogenous growth factors on the formation of scars and ulcers after trauma or burn.. The amounts of endogenous epidermal growth factor (EGF), tumor necrosis factor(TNF) and nitric oxide (NO) in scar and the developing granulation tissues after trauma or burn were determined and their relation with the wound healing were studied.. The results showed that EGF, TNF and NO could be found in all scars and the granulation tissues, but their concentration varied with different tissues, sex and age of patients. In male patients or youngsters, the amounts of EGF, TNF and NO in scars were much greater than those in granulation tissues.. The results indicated that the growth factors are necessary for wound healing, but insufficiency or overproduction of the endogenous growth factors may lead to the development of chronic ulcers or scar formation after trauma or burn.

Topics: Adult; Burns; Cicatrix; Epidermal Growth Factor; Female; Humans; Male; Nitric Oxide; Tumor Necrosis Factor-alpha; Wound Healing

Wound contraction is an important component of healing but, in the extreme, may lead to excessive scar formation and pathological wound contracture. Fetal rabbit wounds heal without contraction or scarring, whereas excisional fetal sheep wounds have been shown to contract, but no scarring or pathological wound contracture is noted. We used an in vitro model, the fibroblast-populated collagen lattice, to study the ability of fetal fibroblasts to coordinate contraction of a collagen matrix and the modulating effects of epidermal growth factor and transforming growth factor-beta 1 on this contraction. With increasing gestational age, fibroblasts increased the degree of collagen lattice contraction. Epidermal growth factor inhibited contraction by fetal fibroblasts, whereas transforming growth factor-beta 1 stimulated it. These findings suggest that while intrinsic differences between fetal and adult fibroblasts exist, polypeptide growth factors may operate at the site of tissue repair to alter cell phenotype. Further work is underway to delineate the role of soluble protein factors responsible for the absence of scarring and contracture seen in the fetal wound.

Topics: Animals; Cicatrix; Collagen; Epidermal Growth Factor; Female; Fetus; Fibroblasts; Gestational Age; In Vitro Techniques; Polyvinyl Alcohol; Pregnancy; Prenatal Injuries; Sheep; Skin; Transforming Growth Factor beta; Wound Healing

Various growth factors are known to play important roles in wound healing, especially in an early inflammatory phase. However, their roles in subsequent scar formation phase are relatively unexplored. The aim of this study is to investigate the mechanisms of regulation in scar formation by these factors. Scar fibroblasts (SF) were obtained from immature scar tissue made at rat hard palate 1 month after excision and normal fibroblasts (NF) were obtained from the palatal mucosa of untreated control animals. SF showed a longer doubling time, and increased level of protein synthesis when compared to NF. Platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) stimulated [3H]-thymidine uptake less effectively in SF than in NF. In both cells, transforming growth factor-beta 1 (TGF-beta 1) inhibited EGF-induced stimulation of [3H]-thymidine uptake, but had no effects when it was added alone. TGF-beta 1 increased collagen synthesis more effectively in SF than in NF. These data indicate that the growth factors may play key roles in regulating proliferation and metabolic activity of fibroblasts during scar formation.

Topics: Animals; Cell Division; Cells, Cultured; Cicatrix; Collagen; DNA Replication; Epidermal Growth Factor; Fibroblasts; Growth Substances; Kinetics; Male; Mouth Mucosa; Platelet-Derived Growth Factor; Protein Biosynthesis; Rats; Rats, Inbred Strains; Transforming Growth Factor beta; Wound Healing

Topics: Angiogenesis Inducing Agents; Animals; Antigens; Biocompatible Materials; Blood Platelets; Burns; Cicatrix; Collagen; Epidermal Growth Factor; Fibroblast Growth Factors; Fluorescent Antibody Technique; Granulocytes; Growth Substances; Humans; Hypertrophy; Inflammation; Laminin; Leukocytes; Macrophages; Pulmonary Fibrosis; Rabbits; Silicone Elastomers; Wound Healing; Wound Infection