GLYCOPROTEINS in Visual Studio .NET

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Glycoproteins (GP) influence cell migration, adhesion, and orientation Fibronectin and tenascin are the GPs most relevant in the dermis although vitronectin, thrombospondin, and epi-
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function, and adhesion Its structure is identical, whether it is derived from bacterial cultures, animals, or humans (Fig 2-6) HA appears freely in the dermis and is more concentrated in areas where cells are less densely packed In young skin, HA is found at the periphery of collagen and elastin fibers and at the interface of these types of fibers These connections with HA are absent in aged skin41 HA is a popular ingredient in cosmetic products because it acts as a humectant Several types are also available in an injectable version for the treatment of wrinkles (see 23) HA appears to also play a role in keratinocyte differentiation and formation of lamellar bodies via its interaction with CD44,42 a cell surface glycoprotein receptor with HA binding sites43 45 Decorin is a member of the small leucine-rich proteoglycans (SLRPs) found in the extracelluar matrix protein Its name is derived from its apparent decorating of collagen fibers Decorin contains a core protein with a high content of leucine repeats and GAG chains of dermatan or chondroitin sulfate It is shaped in a horseshoe pattern and binds to collagen fibrils, resulting in their proper organization46 Decorin-deficient mice have shown clinical skin fragility and irregular collagen fibrils with increased interfibrillar space on histology47 In addition to collagen fibrillogenesis, decorin interacts with fibronectin48 and fibrinogen,49 thereby playing a role in wound healing and hemostasis Another interesting function of decorin is that it reduces the proliferation of cells in neoplasms by stopping their growth in the G1 phase of the cell cycle50 Carrino et al51 studied the catabolic fragment of decorin in adult skin They noted a higher content of the altered decorin in adult dermis as opposed to nonmeasurable amounts in fetal skin and named it decorunt Decorunt was shown to have a lower affinity for collagen fibrils This finding may explain some of the changes related to collagen disorganization in aging skin
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CHAPTER 2 BASIC SCIENCE OF THE DERMIS 11
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MATRIX METALLOPROTEINASES
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The ECM architecture of human skin is based on its continuous remodeling This process requires ECM-degrading enzymes followed by synthesis and deposition of new molecules The matrix metalloproteinases (MMPs), which include a large family of zincdependent endopeptidases, are crucial to the turnover of ECM components Interstitial collagenase, or MMP-1, was the first enzyme discovered in this group MMP-1 is secreted from the fibroblasts and is mainly involved in the degradation of collagen types I, II, and III, but has been shown to also cleave the anchoring fibrils of collagen VII52 Human neutrophil collagenase (MMP8), another type of collagenase, is engaged in cleaving collagen types I and III Collagenase 3 (MMP-13) is the third member of this group of enzymes, and it is known to fragment fibrillar collagens It is also believed to have a role in scarless wound healing53 by enhancing fibroblast proliferation and survival54 Gelatinases are another class of MMPs and consist of two types of enzymes, gelatinase A (MMP-2) and gelatinase B (MMP-9), that are responsible for attacking gelatin and collagen IV in the basement membrane Other groups of MMPs include stromelysins, which are mainly involved in degradation of proteoglycans, laminins, collagen IV, and matrilysin, which is expressed on stromal tissue, fetal skin, and in the setting of carcinomas55 The activity of MMPs is regulated by an endogenous tissue inhibitor of metalloproteinases (TIMPs) TIMPs are naturally produced proteins that specifically inhibit the MMPs The balance between MMPs and their inhibition by TIMPs leads to proper tissue remodeling TIMPs are regulated via expression of cytokines (such as IL-1), growth factors, and even retinoids56,57 Retinoids have been shown to provoke a two- to threefold increase in the biosynthesis of human fibroblast-derived TIMP in vitro58 Increased production of MMPs and decreased production of TIMPs have a role in the metastatic behavior of tumors Synthetic inhibitors of MMPs are of interest to researchers especially in the area of cancer research These inhibitors, such as hydroxamates, contain a zinc-chelating group that binds to the active site of MMPs leading to its inhibition Currently, their use is mostly limited to research studies because of their side-effect profile Certain medications such as doxycycline are also
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known for their inhibitory effect on MMPs and have been studied in myriad MMP-related conditions such as periodontal and atherosclerotic diseases
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