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Growth factors can be classified into two groups: proliferative and differentiative factors Proliferative factors engender more DNA synthesis and result in proliferation of the cells Differentiative factors inhibit the production of DNA and suppress growth, thereby resulting in differentiation of the keratinocytes Epidermal growth factor (EGF) is one of the integral chemokines in the regulation of growth in human cells It binds to the epidermal growth factor receptor (EGFR) located on the basal and suprabasal cells in the epidermis and activates tyrosine kinase activity, which ultimately results in proliferation of the cells19 Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, also has a proliferative effect via the tyrosine kinase receptor on epidermal cells20 It has been shown that KGF contributes to and enhances wound healing21 In addition, KGF has been demonstrated to enhance hyaluronan synthesis in the keratinocytes22 Other important growth factors include the polypeptide transforming growth factors, which consist of two types: Transforming growth factor alpha (TGF- ) and transforming growth factor beta (TGF- ) They differ in both configuration and function TGF- is a proliferative factor, similar to EGF, and works by stimulating a tyrosine kinase response TGF- , which includes three subtypes (1 3), is a differentiative factor with a serine/
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The Cell Cycle
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The above keratinization process is also referred to as the cell cycle The normal cell cycle of the epidermis is from 26 to 42 days17 This series of events, known also as desquamation, normally occurs invisibly with shedding of individual cells or small clumps of cells Disturbances of this process may result in the accumulation of partially detached keratinocytes, which cause the clinical findings of dry skin Disease states may also alter the cell cycle For example, psoriasis causes a dramatic shortening of the cell cycle, resulting in the formation of crusty cutaneous eruptions The cell cycle lengthens in time as humans age18 This means that the cells at the superficial layer of the SC are older and their function may be impaired Results from such compromised functioning include slower wound healing and a skin appearance that is dull and lifeless Many cosmetic products such as retinol and alpha hydroxy acids are believed to
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MOISTURIZATION OF THE SC
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The main function of the SC is to prevent TEWL and regulate the water balance in the skin The two major components that allow the SC to perform this role are lipids and the NMF
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BOX 1-2 Filaggrin, named for lament aggregating protein, derived its name from the fact that it binds keratin laments to form a structural matrix in the SC Genetic defects in the laggrin gene are known to play a role in a subset of ichthyosis vulgaris cases38 Interestingly, laggrin is not present in the super cial layers of the SC Studies have shown that it is completely degraded into amino acids within 2 to 3 days of pro laggrin formation and its constituents are further metabolized to form the NMF40 This is nature s way of keeping its water-binding capabilities in the top layer of the SC where they are needed while preventing the lower layers of the SC from being disrupted by having too much water present In addition, the level of NMF is regulated by the water activity present in the SC
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require such conditions to function The importance of NMF is clear when one notes that ichthyosis vulgaris patients, who have been shown to lack NMF, manifest severe dryness, and scaling of the skin38 It has been demonstrated that normal skin exposed to normal soap washing has significantly lower levels of NMF when compared to normal skin not washed with surfactants39 NMF levels have also been reported to decline with age, which may contribute to the increased incidence of dry skin in the elderly population (see 11)
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