الفهرس | Only 14 pages are availabe for public view |
Abstract Psoriasis is a common, genetically determined, chronic inflammatory and hyperproliferative skin disease with no sex predilection. The immune system has a prominent role in development of this disease. A possible role of growth factors in the pathogenesis of psoriasis is suggested through its effect on keratinocytes proliferation. Growth factors are defined as polypeptides that stimulate cell proliferation through binding to specific high affinity cell membrane receptors present at the target cell surface by a receptor mediated endocytosis. In healthy adults they act via paracrine mechanism, while in neoplastic cells they act through autocrine stimulation of growth. Cells of most tissue types are targets of growth factors, which mediate their effect via receptors with intrinsic tyrosine kinase activity. Epidermal growth factor (EGF) is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation. It also increases cancer risk. Human EGF is a 6045-Da protein with 53 amino acid residues and three intramolecular disulfide bonds. Epidermal growth factor (EGF) is a low molecular weight polypeptide mitogen growth factor that increases the growth and persistence of cells of epithelial (ectodermal) and endodermal origin in vivo and induces growth of epithelial cells and fibroblasts in vitro, It is formed in the submaxillary gland and kidney tubules and is present in nanograms quantities in the plasma. EGF acts by binding with high affinity to epidermal growth factor receptor (EGFR) on the cell surface and stimulating the intrinsic protein-tyrosine kinase activity of the receptor In this study, we measured EGF and epidermal thickness in the lesions of psoriatic patients and in non lesional skin and for volunteers Results were compared to evaluate its role in the pathogenesis of psoriasis. The study was conducted on 30 cases, 20 psoriasis vulgaris patients, and 10 healthy volunteers; all cases were subjected to complete history taking, clinical examination (including PASI score for psoriasis patients) and skin biopsies. A 4 mm punch skin biopsies were obtained from the lesional and non lesional skin of psoriasis, while 2 biopsies were taken from control group from apparently healthy skin. Estimation of tissue level of EGF was done by quantitative PCR. Epidermal thickness was measured. By measuring tissue level of EGF, our data revealed that EGF was higher in lesional than in non lesional skin and the difference was statistically significant (p<0.001). Both lesional and non lesional EGF was higher than control group and the difference was significant (P<0.001). The difference of epidermal thickness was not significant between non lesional skin and control group, while it was highly significant between lesional and non lesional P<0.001, and between lesional and control group P<001. Also, correlation of EGF and epidermal thickness was highly significant P<0.001. We concluded that the elevated level of EGF in psoriatic play an important role in pathogenesis of psoriasis possibly through its hyperproliferative effect on keratinocytes. In conclusion, our findings indicate that EGF serve as an important regulator of cellular growth, proliferation and differentiation in psoriasis, and this may show a unique patterns for specific dermatoses and are not universally elevated in all skin diseases associated with abnormal cellular proliferation and/or differentiation. It is not clear if the rise in the level of EGF reflect the consequence of the disease or the cause of the disease. Further studies to determine factors that regulate EGF expression may yield important new insights into the pathogenesis of specific skin diseases and this could help in generating a spectrum of new therapeutic pattern specifically designed to target EGF or its receptors in such diseases. |