Biologie de la peau https://biologiedelapeau.fr/ fr SPIP - www.spip.net DERMIS http://biologiedelapeau.fr/spip.php?article6 http://biologiedelapeau.fr/spip.php?article6 2011-04-28T21:33:00Z text/html en <p align=justify>The dermis is one of the constitutive layers of the skin between the epidermis and subcutaneous tissues; it is composed of two layers, the papillary dermis lying immediately below the epidermis and the reticular dermis accounting for the largest part of the dermis. It is a 2 to 4 mm-thick layer of connective tissue mainly composed of extracellular matrix (ECM) produced by fibroblasts.</p> <p align=justify>The dermis houses the neural, vascular, lymphatic systems, and epidermal appendages including excretory and secretory glands (sebaceous, eccrine and apocrine glands), hair follicles, and nails. Neural structures include sensory nerve receptors of Merkel and Meissner's corpuscles (for touch), Pacinian corpuscles (for pressure), and Ruffini corpuscles (mechano-receptors). The dermis also hosts multifunctional cells of the immune system such as dendritic dermal cells, macrophages and mast cells .</p> - <a href="http://biologiedelapeau.fr/spip.php?rubrique5" rel="directory">Dermis</a> <div class='rss_texte'><div class="cs_sommaire cs_sommaire_sans_fond" id="outil_sommaire"> <div class="cs_sommaire_inner"> <div class="cs_sommaire_titre_sans_fond"> Table of contents </div> <div class="cs_sommaire_corps"> <ul> <li><a title="1. Resident cells of the dermis" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_0">1. Resident cells of the dermis</a></li> <li><a title="1.1 Fibroblasts" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_1">1.1 Fibroblasts</a></li> <li><a title="1.2 Resident dermal cells of the immune system" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_2">1.2 Resident dermal cells of the immune system</a> <ul> <li><a title="1.2.1 Macrophages" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_3">1.2.1 Macrophages</a></li> <li><a title="1.2.2 Dermal dendritic cells" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_4">1.2.2 Dermal dendritic cells</a></li> <li><a title="1.2.3 Plasmacytoid dendritic cells" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_5">1.2.3 Plasmacytoid dendritic cells</a></li> <li><a title="1.2.4 Mast cells" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_6">1.2.4 Mast cells</a></li></ul></li> <li><a title="2. The ExtraCellular Matrix (ECM)" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_7">2. The ExtraCellular Matrix (ECM)</a></li> <li><a title="3. The extrafibrillar matrix" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire_8">3. The extrafibrillar matrix</a></li> </ul> </div> </div> </div><p align=justify>The dermis is one of the three constitutive layers of the skin, situated between the <a href='http://biologiedelapeau.fr/spip.php?mot6' name='mot6_0' class='cs_glossaire'><span class='gl_mot'>epidermis</span><span class="gl_js" title="Epidermis<br />epidermis"> </span><span class="gl_jst" title="The epidermis is the outermost portion of the skin. It is a continually renewing stratified (= several layers), squamous epithelium. The keratinocytes (= keratin-producing cells) are the main epidermal cell type (90 to 95 %). The other epidermal cells include melanocytes, Langerhans cells and Merkel cells."> </span></a> and the <a href='http://biologiedelapeau.fr/spip.php?mot23' name='mot23_1' class='cs_glossaire'><span class='gl_mot'>hypodermis</span><span class="gl_js" title="hypodermis<br />subcutaneous fat<br />panniculus adiposus)"> </span><span class="gl_jst" title="The hypodermis represents the deepest part of the skin separating it from the underlying aponevroses or the periosteum. It is an adipose tissue mainly made of adipocytes organized into primary and secondary lobules defined by septa of fibrous connective tissue containing nerves, blood vessels, and lymphatics. Adipocytes are large (up to 100 mum), rounded cells with a lipid-laden cytoplasm (triglycerides, fatty acids) compressing the nucleus against the cell membrane.<br />The hypodermis play a major role in the thermoregulation by insulating the body; it is also a reserve energy supply; it cushions and protects the skin allowing its mobility over underlying structures. Moreover, it has a cosmetic effect in molding contours of our body."> </span></a>, and is composed of two layers, the papillary dermis lying immediately below the epidemis and the reticular dermis. It is a 2 to 4 mm-thick layer of connective tissue mainly composed of extracellular matrix (ECM) produced by fibroblasts. </p> <p align=justify>The dermis houses vascular and lymphatic vessels, nerves and specialised neural receptors which include sensory nerve receptors of Merkel and Meissner's corpuscles (for touch), <a href='http://biologiedelapeau.fr/spip.php?mot38' name='mot38_2' class='cs_glossaire'><span class='gl_mot'>Pacinian corpuscles</span><span class="gl_js" title="Pacinian corpuscles"> </span><span class="gl_jst" title="Pacinian corpuscles: is a class of rapidly adapting (phasic) mechanoreceptors that detect gross pressure changes and vibrations. It is is oval shaped and approximately 1 mm in length and is wrapped by a layer of connective tissue. It contains 20 to 60 concentric lamellae composed of fibrous connective tissue and fibroblasts, separated by gelatinous material. The lamellae are very thin, flat, modified Schwann cells. In the center of the corpuscle is the inner bulb, a fluid-filled cavity with a single afferent unmyelinated nerve ending."> </span></a> (for pressure), and <a href='http://biologiedelapeau.fr/spip.php?mot37' name='mot37_3' class='cs_glossaire'><span class='gl_mot'>Ruffini corpuscles</span><span class="gl_js" title="Ruffini corpuscles"> </span><span class="gl_jst" title="Ruffini corpuscles is a class of slowly adapting mechanoreceptor thought to exist only in the glabrous dermis and subcutaneous tissue of humans. It is sensitive to skin stretch, and contributes to the kinesthetic sense of and control of finger position and movement. It is believed to be useful for monitoring slippage of objects along the surface of the skin, allowing modulation of grip on an object."> </span></a> (mechano-receptors). The dermis contains also epidermal appendages including eccrine and apocrine sweat glands, pilo-sebaceous follicles. The dermis also hosts multifunctional cells of the immune system such as dendritic dermal cells, <a href='http://biologiedelapeau.fr/spip.php?mot91' name='mot91_4' class='cs_glossaire'><span class='gl_mot'>macrophages</span><span class="gl_js" title="macrophage<br />macrophages"> </span><span class="gl_jst" title="Les macrophages sont dérivés de la moelle osseuse. Ils se différencient en monocytes dans le sang, puis en macrophages dans le derme où ils perdent leur potentiel prolifératif. Ils ont la capacité de phagocyter les débris cellulaires et les pathogènes, de les digérer ou de les appréter et de présenter les antigénes apprétés aux lymphocytes et autres cellules immunitaires pour déclencher une réponse immunitaire spécifique. Les macrophages secrétent également une large gamme de facteurs impliqués dans la régulation des réponses immunitaires et le développement de l'inflammation ; ils peuvent produire des enzymes hydrolytiques, des composants du système du complément, et une large gamme de facteurs solubles tels que l'interleukine-1, certaines prostaglandines, de l'interféron, et des facteurs de croissance. Ils expriment à leur surface des récépteurs pour des lymphokines qui induisent leur activation."> </span></a> and <a href='http://biologiedelapeau.fr/spip.php?mot52' name='mot52_5' class='cs_glossaire'><span class='gl_mot'>mast cells</span><span class="gl_js" title="Mast cell<br />mast cell<br />mast cells<br />Mast cells"> </span><span class="gl_jst" title="Mast cells are roundish or spindled specialized secretory cells that contains many metachromatic granules. They are present throughout the dermis but found most commonly around blood vessels, pilosebaceous apparatus and in the subcutaneous fat (hypodermis). Their granules are rich in histamine and heparin and contains also various enzymes including eosinophil chemotactic factors of anaphylatoxis (ECF-A), neutrophil chemotactic factor (NCF), chymase, tryptase and TNF-like substance. They also produce and release prostaglandins, leukotrienes, and platelet-activating factors. Mast cells respond to physical stimuli (ligth, cold, heat, acute trauma, vibration, and sustained pressure), chemical and immunologic stimuli by releasing the content of their secretory granules. The granule release firstly induces vasodilatation, dermal edema then an infiltration into the dermis of inflammatory cells (neutrophils, eosinophils and basophils), attracted by the released chemotactic factors. Mast cells are the sentinel cell in immediate-type hypersensitivity reactions and are also involved in the production of subacute and chronic inflammatory diseases. Mastocytes stain red-violet with toluidin blue and methylene blue stains, and immunohistochemically with antibodies to chymase and tryptase. They also express the c-kit protein."> </span></a> .</p> <p align=justify>The dermis is divided into two functional layers, the papillary dermis and reticular dermis which differ in both the composition and organization of their respective extracellular matrices. The reticular dermis is characterized by thick well-organized fiber bundles which contrast with the thin, poorly organized collagen fiber bundles of the papillary dermis, consisting primarily of type I and type III collagens. Collagen fiber bundles in the papillary dermis contain more type III collagen than do those in the reticular dermis</p> <h3 class="spip" id="outil_sommaire_0"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a><i>1. Resident cells of the dermis</i></h3><p align=justify>Cells are more numerous in the papillary dermis than in the reticular dermis and form two sub-populations. The first one includes the fibroblasts and the <a href='http://biologiedelapeau.fr/spip.php?mot80' name='mot80_6' class='cs_glossaire'><span class='gl_mot'>fibrocytes</span><span class="gl_js" title="Fibrocytes<br />fibrocytes<br />fibrocyte"> </span><span class="gl_jst" title="Fibrocytes originate from the BM and are considered to be a newly identified leukocyte subpopulation that has been found in the peripheral blood, wound sites, and areas of tissue remodeling."> </span></a> which, by producing the extracellular matrix, supply the basic structure of the dermis. The second one consists of hematopoietic cells, namely the dermal dendritic cells, the macrophages and the mast cells which are dermal representatives of the immune system.</p> <h3 class="spip" id="outil_sommaire_1"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.1 Fibroblasts</h3><p align=justify>Fibroblasts are the main cells of the dermis and represent a heterogeneous population of cells with distinct patterns of synthetic activities and functions (<a href="http://jcs.biologists.org/content/117/5/667.full.pdf+html" class='spip_out' rel='external'>Sorrell and Caplan, 2004</a>), and the conventional understanding of these cells, which is based largely on cell morphology is inadequate. In addition to fibroblasts that remain during embryonic development, BM appears to be an important source that provides ‘‘fibroblasts'' to the skin in adults, which may include, but is not limited to, CD45-negative mesenchymal <a href='http://biologiedelapeau.fr/spip.php?mot73' name='mot73_7' class='cs_glossaire'><span class='gl_mot'>stem cells</span><span class="gl_js" title="Stem cell<br />stem cell<br />stem cells"> </span><span class="gl_jst" title="A stem cell is a cell that possesses two properties:<br />it can self-renew to produce more stem cell<br />it can differentiate into diverse specialized cell types."> </span></a> (BM-MSCs), CD45-positive fibrocytes and endothelial progenitor cells (EPCs ). The role of these newly discovered components of ‘‘fibroblasts'' in the dermis are not fully understood. BM-MSCs and EPCs are thought to enhance cutaneous repair/regeneration and fibrocytes appear to cause fibrosis and are probably involved in hypertrophic scar formation.</p> <p>Three subpopulations of dermal fibroblasts have been defined according to their location in the papillary dermis, in the reticular dermis or associated with the hair follicle, lying in the dermal papilla or along its shaft. In cell culture, papillary fibroblasts divide at faster rates than do site-matched reticular fibroblasts. Reticular dermal fibroblasts seeded into type I collagen lattices contract them faster than do papillary dermal fibroblasts. In monolayer culture, at confluence, papillary fibroblasts attain a higher density than do reticular fibroblasts.</p> <p align=justify>The proteoglycan <a href='http://biologiedelapeau.fr/spip.php?mot60' name='mot60_8' class='cs_glossaire'><span class='gl_mot'>decorin</span><span class="gl_js" title="Decorin<br />decorin"> </span><span class="gl_jst" title="Decorin belongs to the family of small leucine-rich proteoglycans that harbors one chondroitin/dermatan sulfate side chain at its N terminus. It was originally named because of its ability to “decorate” collagen fibrils, thereby regulating fibrillogenesis, a key mechanism of matrix assembly and homeostasis. Decorin binds to type I collagen and stabilizes the structure of the extracellular matrix. Decorin interacts also with fibronectin, thrombospondin and the complement component C1q.<br /><br />It suppresses cellular proliferation, is strongly expressed in quiescent post-confluent fibroblasts and rarely expressed within actively proliferating or transformed tissues.<br /> <br />Decorin contains leucine-rich repeats (=matrikines) able to bind EGF receptor (Kd 27-887 nM), thereby triggering a signaling cascade that initially leads to phosphorylation of mitogen-activated protein (MAP) kinase, induction of p21, and growth suppression. This activation eventually results in a decrease of EGFR levels and nearly complete suppression of EGFR autophosporylation.<br /><br />Decorin regulates the TGF-β signaling pathway. Decorin suppresses tumor cell–mediated angiogenesis by inhibiting the endogenous production of vascular endothelial cell growth factor. Decorin binds directly and with high affinity (Kd = 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF) and suppresses intracellular levels of β-catenin, a known downstream Met effector, and thereby inhibits Met-mediated cell migration and growth.<br /><br />During skin repair, decorin would function as a quiescence signal inducing decrease of migration, proliferation and extracellular matrix production by fibroblasts when the wound has reached its mature state.<br /><br /><strong>Bibliography</strong><br /><br /><a href="http://en.wikipedia.org/wiki/Decorin" class="spip_out" rel="external">Decorin Wikipedia</a><br /><br /><a href="http://www.jbc.org/content/275/42/32879.long" class="spip_out" rel="external">Csordás G, Santra M, Reed CC, Eichstetter I, McQuillan DJ, Gross D, Nugent MA, Hajnóczky G, Iozzo RV. Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo. J Biol Chem. 2000 Oct 20;275(42):32879-87.</a><br /><br /><a href="http://jcb.rupress.org/content/185/4/743.full.pdf+html" class="spip_out" rel="external">Goldoni S, Humphries A, Nyström A, Sattar S, Owens RT, McQuillan DJ, Ireton K, Iozzo RV. Decorin is a novel antagonistic ligand of the Met receptor. J Cell Biol. 2009 May 18;185(4):743-54.</a>"> </span></a> is intensely expressed in the papillary dermis but is dispersed between collagen fiber bundles in the reticular dermis. In monolayer cultures, papillary dermal fibroblasts secrete significantly more decorin and contain more decorin mRNA than did corresponding reticular cells. By contrast, the two cellular populations produce identical amounts of biglycan.</p> <p align=justify>The main function is to synthesize or degrade the extracellular matrix and the extrafibrillar matrix; they also play a key role in dermo-epidermal interactions. It has been shown that the same fibroblast is able to synthesize more than one type of collagens and elastin simultaneously.</p> <p align=justify>Fibroblasts cooperate with keratinocytes to organise the dermal-epidermal junction. Both produce type IV collagen, a major component of the lamina densa and type VII collagen the main component of the anchoring fibrils. The fibroblasts is also a major source of <a href='http://biologiedelapeau.fr/spip.php?mot56' name='mot56_9' class='cs_glossaire'><span class='gl_mot'>entactin</span><span class="gl_js" title="Nidogen<br />nidogen<br />Entactin<br />entactin<br />nidogen-1<br />Nidogen-1"> </span><span class="gl_jst" title="The nidogen family, representing multivalent matrix binding proteins, consists in mammals of two members, nidogen-1 and -2. They are considered as classical linkers joining laminin and collagen IV networks in basement membranes. Nidogen-1 also named Entactin is an integral and ubiquitous component of the basement membrane."> </span></a>/nidogen.</p> <h3 class="spip" id="outil_sommaire_2"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.2 Resident dermal cells of the immune system </h3><h4 class="spip" id="outil_sommaire_3"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.2.1 Macrophages</h4><p align=justify>Macrophages are derived from the bone marrow. They differentiate into monocytes in the blood, then become terminally differentiated in the dermis as macrophages with no more ability to divide. They are able to phagocyte cellular debris and pathogens, process (digest) them and present antigens to lymphocytes and other immune cells to trigger a specific immune response. Macrophages are also secretory cells vital for the regulation of immune responses and the development of <a href='http://biologiedelapeau.fr/spip.php?mot219' name='mot219_10' class='cs_glossaire'><span class='gl_mot'>inflammation</span><span class="gl_js" title="inflammation"> </span><span class="gl_jst" title="L'inflammation est un ensemble de réactions générées par l'organisme en réponse à une agression : plaie, infection, allergie, ... ."> </span></a>; they produce hydrolytic enzymes, components of the complement system, and a variety of soluble factors such as interleukin-1, certain prostaglandins, interferon, growth promoting factors, .... They also express at their surface receptors for lymphokines that allow their activation.</p> <h4 class="spip" id="outil_sommaire_4"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.2.2 Dermal dendritic cells</h4><p align=justify>Dermal dendritic cells (DDC) were identified more than 120 years after LCs were discovered. Initially, DDC were identified using a polyclonal antibody against clotting factor XIIIa and thought to be a homogeneous population. Dermal DCs are located in the deeper dermis. They typically express the C-type lectin, CD 209 (DC-SIGN), and CD11b, both of them are absent from <a href='http://biologiedelapeau.fr/spip.php?mot156' name='mot156_11' class='cs_glossaire'><span class='gl_mot'>Langerhans cells</span><span class="gl_js" title="Langerhans cells<br />Langerhans cell"> </span><span class="gl_jst" title="Langerhans cells which represent 3-6% of all cells in the epidermis, are mobile, dendritic, antigen presenting cells with a stellate appearance which reside in the suprabasal layers of the epidermis wedged in between, and in close contact with keratinocytes. Langerhans cells are derived from a mobile pool of bone marrow -derived precursors and constitute, in normal epidermis, a stable self-reproducing cell population throughout life under steady-state conditions. LCs are antigen presenting cells that may play a role either in triggering cutaneous immune activation or in sustaining cutaneous immunological tolerance depending of the environmental context."> </span></a>.<br class='autobr' /> Dermal, dendritic, antigen-presenting cells may elicit immune responses to cutaneous or circulating antigens and may form an important second line of defense behind epidermal Langerhans cells.</p> <p align=justify>Dermal dendritic cells have the capacity to take up cutaneous antigens, mature and migrate to draining local lymph nodes, and present these antigens to T cells and B cells.. This process may be essential during skin infections, such as herpes simplex, as blockade of dermal DC migration from skin to lymph node may prevent effective cytotoxic T cell activation.</p> <h4 class="spip" id="outil_sommaire_5"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.2.3 Plasmacytoid dendritic cells</h4><p align=justify>Plasmacytoid dendritic cells (PDCs) are an additional unique population of resident cutaneous DCs. They have a morphology, which is similar to a plasma cell and share many characteristics with B cells, including dependence on a B cell transcription factor (SPI-B), and immunoglobulin gene rearrangements. Both PDCs and myeloid DCs may arise from a bone marrow-derived common DC precursor. Plasmacytoid DCs express high levels of HLA-DR, have the capacity to present antigen, and are characterized by their ability to produce large amounts of type 1 interferon (IFN-α, β, ω) during viral infection (10,000 fold more IFN than any other cell type).</p> <h4 class="spip" id="outil_sommaire_6"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>1.2.4 Mast cells</h4><p align=justify>Mast cells are specialized secretory cells that contains many granules rich in <a href='http://biologiedelapeau.fr/spip.php?mot221' name='mot221_12' class='cs_glossaire'><span class='gl_mot'>histamine</span><span class="gl_js" title="histamine"> </span><span class="gl_jst" title="L'histamine est un médiateur préformé synthétisé par les plaquettes puis par les mastocytes et les basophiles ; elle joue un rôle majeur dans l'augmentation de la perméabilité vasculaire et la relaxation vasculaire."> </span></a> and heparin and are present throughout the dermis but found most commonly around blood vessels, pilosebaceous apparatus and in the subcutaneous fat (hypodermis).</p> <p align=justify>Mast cells respond to physical stimuli (ligth, cold, heat, acute trauma, vibration, and sustained pressure), chemical and immunologic stimuli by releasing the content of their secretory granules. The granule release firstly induces vasodilatation, dermal edema then an infiltration into the dermis of inflammatory cells (neutrophils, eosinophils and basophils), attracted by the released chemotactic factors. Mast cells are the sentinel cell in immediate-type hypersensitivity reactions and are also involved in the production of subacute and chronic inflammatory diseases.</p> <p align=justify>Mast cells stain metachromatically with toluidin blue stain, and immunohistochemically with antibodies to chymase and tryptase. They also express the c-kit protein. At the ultrastructural level, the granules can be easily separated into secretory and lysosomal granules.</p> <h3 class="spip" id="outil_sommaire_7"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>2. The ExtraCellular Matrix (ECM)</h3><p align=justify>The extracellular matrix is a complex structure composed of highly organized collagen, elastic, and reticular fibers.</p> <p align=justify>Type I collagen is by far the most abundant protein in human skin, comprising greater than 90% of its dry weight. Fibrillar collagens type I, III, and V self assemble into larger collagen fibers that form a three dimensional structural network throughout the dermis and provide the skin with tensile strength and tissue integrity. The collagen network is organized and maintained by dynamic mechanical tension provided by the fibroblasts responsible for its production .</p> <p>All fibrillar collagens consist of three polypeptide chains wound around each other in a triple helical configuration. Each polypeptide chain is originally synthesized with additional amino acids at both ends that confer solubility. The soluble triple helix, which is termed procollagen, is assembled inside fibroblasts. Procollagen is secreted from fibroblasts, and the peptide ends are removed by two enzymes in the extracellular space. Removal of the ends produces collagen, which spontaneously assembles into large fibers that are enzymatically cross-linked.</p> <p align=justify><strong>Elastic fibres</strong>, responsible for the retractile properties of the skin, can be visualised with histochemical stains (orcein). Three different classes of elastic fibre, named oxytalan fibres, elaunin fibres, or elastin fibres have been distinguished according to their content in microfibrils, made of fibrillin, and in elastin, an additional amorphus component . Oxytalan fibres are localised in the papillary dermis and contains only microfibrils (10–12 nm across). They form arborisations that are perpendicular to the dermal-epidermal junction. Elaunin fibres and elastin fibres contain respectively either a little or a lot of additional amorphous components. Elaunin fibers are organised in a sub-papillar plexus that runs horizontally and is anastomosed with the oxytalan fibers and the thicker elastin fibers of the reticular dermis.</p> <p align=justify>It is elastin that provides elasticity and resiliency of the elastic fibers and helps skin to return to its original position when it is poked or pinched. The microfibrillar part of the elastic fibre is composed principally of fibrillin-1a large glycoprotein more than 2800 amino acids long and with Ca2+ binding repeats that aid stabilization of the molecule. Elastic fibres are designed to maintain elastic function for a lifetime. However, various enzymes (matrix metalloproteinases and serine proteases) are able to cleave elastic fibre molecules. Indeed, loss of elasticity due to degradative changes is a major contributing factor in degenerative changes in sun-damaged skin.</p> <p align=justify>The reticular fibers are fibers composed of type III collagen that are observed in histology after a silver staining, at the dermal-epidermal junction and in the basal lamina of blood vessels, nerves and adipocytes.</p> <h3 class="spip" id="outil_sommaire_8"><a title="Table of contents" href="http://biologiedelapeau.fr/spip.php?page=backend&id_rubrique=5#outil_sommaire" class="sommaire_ancre"> </a>3. The extrafibrillar matrix</h3><p align=justify>The dermal material lying outside the<br class='autobr' /> cells, and not consisting of either collagen fibres or elastic<br class='autobr' /> fibres, is called the extrafibrillar matrix, which is extracellular and composed of a complex mixture of proteoglycans, glycoproteins, glycosaminoglycans, water, and hyaluronic acid. Chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, and heparin are the most significant glycosaminoglycans, which, bound to proteins, form the proteoglycans of the skin. <a href='http://biologiedelapeau.fr/spip.php?mot55' name='mot55_13' class='cs_glossaire'><span class='gl_mot'>Versican</span><span class="gl_js" title="versican<br />Versican"> </span><span class="gl_jst" title="Versican, also called PG-M, is a lectican family proteoglycan that is present in the fetal, neonatal, and adult dermis in humans. It is a member of a family of large, aggregating proteoglycans that primarily bear chondroitin sulfate glycosaminoglycan side chains.Versican interacts with both fibrillin-1 and isolated microfibrils. Versican binds fibulin-1 and -2 via its lectin-like domain and localizes to cutaneous microfibrils. Versican also binds to hyaluronic acid (HA) via its N-terminal region and HA is co-distributed with elastic fibers in the dermis. Therefore, by binding to fibrillin microfibrils and HA, versican can impart viscous properties to cutaneous microfibrils. The loss of the HA-binding ability of versican followed by HA exclusion may be responsible for the pathological and phenotypical changes observed in solar elastosis.<br /><br /><a href="http://www.nature.com/jid/journal/v127/n7/pdf/5700754a.pdf" class="spip_out" rel="external">Keiko Hasegawa, Masahiko Yoneda, Hiroko Kuwabara, Osamu Miyaishi, Naoki Itano, Akiko Ohno, Masahiro Zako and Zenzo Isogai (2007). Versican, a Major Hyaluronan-Binding Component in the Dermis, Loses its Hyaluronan-Binding Ability in Solar Elastosis. J Invest Dermatol 127: 1657-1663.</a>"> </span></a> and <a href='http://biologiedelapeau.fr/spip.php?mot51' name='mot51_14' class='cs_glossaire'><span class='gl_mot'>perlecan</span><span class="gl_js" title="Perlecan<br />perlecan"> </span><span class="gl_jst" title="<strong>Perlecan</strong> is a large HSPG, present in virtually all BMs ."> </span></a> are the most important proteoglycans of the skin; versican produced by fibroblasts, smooth muscle cells and epithelial cells is involved in assuring the tautness of the skin; perlecan is found in basement membranes. Other major glycoproteins are laminins, <a href='http://biologiedelapeau.fr/spip.php?mot57' name='mot57_15' class='cs_glossaire'><span class='gl_mot'>matrilins</span><span class="gl_js" title="Matrilin<br />Matrilins<br />matrilin<br />Matrilin"> </span><span class="gl_jst" title="The family of matrilins are typical modular proteins belonging to a superfamily characterized by von Willebrand factor A-like domains. <br /><br /> <br />To date, four different matrilins have been identified, but their biologic role is still largely unknown. Matrilin-1, formerly also named cartilage matrix protein, and matrilin-3 are mainly expressed in cartilage, whereas matrilin-2 and matrilin-4 have been found in a number of different tissues. <br /><br /> <br />Matrilin-2 is expressed in normal skin by keratinocytes and fibroblasts and may thus contribute to cutaneous homeostasis. Matrilin-2 is a widespread extracellular matrix component that can interact with itself and with other both collagenous and non-collagenous matrix molecules. This interaction repertoire, together with its oligomeric structure, renders matrilin-2 a good candidate as an adapter or mediator molecule for interactions between other matrix macromolecules during the assembly of an extracellular matrix. It has the potential to serve such functions in and between basement membranes, microfibrils and in the dermal extracellular matrix.<br /><br /> <br /><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222949/pdf/12180907.pdf" class="spip_out" rel="external">Piecha D, Wiberg C, Mörgelin M, Reinhardt DP, Deák F, Maurer P, Paulsson M (2002).Matrilin-2 interacts with itself and with other extracellular matrix proteins.Biochem J. 367(Pt 3):715-21.</a>"> </span></a>, <a href='http://biologiedelapeau.fr/spip.php?mot59' name='mot59_16' class='cs_glossaire'><span class='gl_mot'>vitronectin</span><span class="gl_js" title="Vitronectin<br />vitronectin"> </span><span class="gl_jst" title="Vitronectin is a multi-functional 75 kDa glycoprotein that is found in the circulation where it contributes to hemostasis by regulating blood coagulation and fibrinolysis; it forms a major component of the extracellular matrix where it plays major roles in cell adhesion, pericellular proteolysis, angiogenesis, tissue invasion and metastasis. <br /><br />Vitronectin binds to a number of ligands including integrin receptors, heparin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), thrombin–anti-thrombin (TAT) complexes, glycosaminoglycans, collagen, complement, and the urokinase plasminogen activator receptor (uPAR) and IGF-II . VN is also involved in the immune defence system through its interaction with the terminal complex of complement.<br /><br /> The insulin-like growth factor (IGF) system plays an important role in a number of disease states, such as cancer and psoriasis, through its ability to modulate cell proliferation, attachment, and migration. Both the IGF-II:VN and IGF-I:IGFBP-5:VN complexes stimulate not only enhanced cell migration, but also enhanced cell protein synthesis in skin keratinocytes.<br /><br /><strong>Bibliography</strong><br /><br /><a href="http://en.wikipedia.org/wiki/Vitronectin" class="spip_out" rel="external">Vitronectin from Wikipedia, the free encyclopedia</a><br /><br /><a href="http://www.jbc.org/content/279/28/29359.full.pdf+html" class="spip_out" rel="external">Mayasundari A, Whittemore NA, Serpersu EH, Peterson CB (2004). &ldquo;The solution structure of the N-terminal domain of human vitronectin: proximal sites that regulate fibrinolysis and cell migration&rdquo;. J. Biol. Chem. 279 (28): 29359–66</a>"> </span></a>, thrombospondins, fibronectin, and <a href='http://biologiedelapeau.fr/spip.php?mot58' name='mot58_17' class='cs_glossaire'><span class='gl_mot'>tenascins</span><span class="gl_js" title="Tenascin<br />tenascin<br />tenascins<br />Tenascins"> </span><span class="gl_jst" title="The tenascins are a highly conserved family of large oligomeric glycoproteins found in the extracellular matrix of vertebrate organisms. Two decades ago, the molecule now known as tenascin-C was among the first proteins shown to have an adhesion modulatory role antagonizing cell attachment to fibronectin. Cells that normally demonstrate a stationary phenotype on the fibronectin-containing matrix by spreading out and forming cortical actin stress fibers will show morphological changes when <strong>tenascin-C</strong> is included in the matrix by extending membrane protrusions and exhibiting decreased stress fiber formation, characteristics more typical of a migratory phenotype. There are currently four tenascin paralogues that have been identified in mammals, each designated with a letter derived, for the most part, from earlier eponyms: C, R, X, and W. Although each type has a distinctive expression pattern, the tenascins share the characteristic of having tightly regulated expression during development and throughout an organism's life. Tenascins also share the characteristic of modulating cell-matrix interactions and mediating a state of matrix attachment that promotes motility while also influencing other cell functions. As such, this protein family has important functions not only during development but also during pathological states in the adult such as tissue injury and tumorigenesis where remodeling processes are promoted.<br /><br />Bibliography<br /><br /><a href="http://www.jbc.org/content/280/29/26641.long" class="spip_out" rel="external">Hsia HC, Schwarzbauer JE. Meet the tenascins: multifunctional and mysterious. J Biol Chem. 2005 Jul 22;280(29):26641-4.</a>"> </span></a>; they are involved in cell adhesion, cell migration, and cell-cell communication.</p> <p>Bibliography</p> <p><a href="http://www.in-cosmetics.com/ExhibitorLibrary/905/Biochemistry_of_Skin_4.pdf" class='spip_out' rel='external'>Desmond J. Tobin: Biochemistry of human skin—our brain on the outside. Chem. Soc. Rev., 2006, 35, 52-67</a></p></div>