GROWTH FACTORS in Visual Studio .NET

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A recent approach to the treatment of aging skin is the use of growth factors The likeness of chronic photodamage to an injury such as a chronic wound that has not progressed to complete repair has led investigators to seek using growth factors for skin rejuvenation94,95 Like chronic wounds, ultraviolet radiation (UVR)-induced skin damage requires regeneration of keratinocytes, broblasts, dermal extracellular matrix, and the microvasculature96 Growth factors are large peptides that have both anabolic and catabolic functions in cutaneous physiology Repair and remodeling of epidermal and dermal tissue is a tightly coordinated process that is largely orchestrated by growth factor proteins Keratinocytes, in ammatory cells, broblasts, and endothelial cells are each affected by the presence or absence of these mediators, and changes in cutaneous morphology can often be traced to instability of this communication network The most well-characterized cutaneous growth factors include epidermal growth factor, broblast growth factor, keratinocyte growth factor, platelet-derived growth factor, transforming growth factor (TGF), and vascular endothelial growth factor These large proteins use autocrine and paracrine signaling to bind cellsurface receptors at low concentrations (10 9 molar) and initiate intracellular signal transduction cascades that stimulate in ammatory cell migration, angiogenesis, keratinocyte replication, broblast proliferation, and synthesis of dermal extracellular matrix material97 It is the synchronous interaction of multiple growth factors that is signi cant, with no one growth factor being a more important determinant of outcome in cutaneous repair94 Advances in cutaneous tissue engineering over the past few decades have provided the ability to arti cially
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construct human skin components that aid in the healing of chronic wounds These replacement tissue grafts, consisting of cells, extracellular matrix components, or both, provide biologically active dressings that synthesize growth factors regulating tissue repair96 Growth factors are critical to the success of any of any skin substitute in inducing wound repair Furthermore, biotechnologic advances in tissue culture have permitted the collection of the endogenous growth factors necessary for cutaneous tissue remodeling and repair95 Culture-borne human growth factors can be concentrated and compounded into topical formulations for use in cosmeceutical applications that treat the effects of chronic photodamage, much as they did in their original use for dermal tissue repair in wounds TGF- is perhaps the best known and most widely used growth factor in cosmeceuticals TGF- refers to a family of multifunctional proteins capable of regulating proliferation, differentiation, tissue remodeling, and repair among various cell types98,99 In the 1980s, pioneering studies were performed introducing TGF- by subcutaneous injection in murine models TGF- induced a dose- and time-dependent increase in broblast proliferation, collagen synthesis, and vasculogenesis Furthermore, marked reduction in collagen synthesis as measured by a decrease in proline incorporation into collagen, was achieved by administration of antibodies to TGF100 These pioneering discoveries provided the foundation for understanding cutaneous growth factors as we know them today TGF- is a peptide hormone consisting of two 12-kDa chains linked by disul de bonds TGF- is secreted by activated broblasts, lymphocytes, and platelets97,100,101 It acts as a positive growth factor upon broblasts and is the most well understood mediator of procollagen, bronectin, and glycosaminoglycan synthesis99 103 TGF- binds to the extracellular domain of the TGF- receptor II (TbRII) transmembrane receptor on broblasts and induces a conformational change in the TbRII s intracellular serine-threonine kinase domain This conformational change triggers a cascade of intracellular events that culminate in the transcription of genes that code for synthesis of dermal extracellular matrix (ECM) material such as collagen, elastin, proteoglycans, and glycosaminoglycans98,99 UV irradiation alters the dermal matrix both quantitatively and qualitatively UV irradiation impairs the interaction of TGF- with the TbRII thereby preventing the cascade of events necessary for broblast synthesis of the dermal ECM The mechanism by which UVA irradiation
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