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Skin; dermis
Functional histology of dermis with collagen and elastic fibers.
Ann Dermatol Venereol. 2008 Jan;135(1 Pt 2):1S5-20. Prost-Squarcioni C, Fraitag S, Heller M, Boehm N. Laboratoire d'Histologie du Pr Salzmann, UFR Léonard de Vinci, 93000 Bobigny, France. catherine.prost@avc.aphp.fr
The skin is composed of epidermis (top in image), dermis and subcutaneous tissue that interconnect anatomically. The dermis is an integrated system of fibrous and amorphous connective tissue that accommodates nerve and vascular networks, epidermally derived appendages, fibroblasts, macrophages and mast cells.
Elastic (dark blue lines) and collagen tissue (pink areas) are the main types of fibrous connective tissue. The elastic connective tissue is assembled in a continuous network including mature elastic fibers, immature elaunin fibers and oxytalan fibers. Mature elastic fibers and elaunin have microfibrillar and amorphous matrix components while oxytalan fibers only contain microfibrils. Several molecules have been identified as constituents of the elastic fibers.
Among the most characterized of these molecules is elastin in amorphous matrix, fibrillins 1 and 2 and LTBP-2 (ligand of latent TGFbeta) in microfibrils and fibulins which interconnect elastin and fibrillins. Elastic fibers provides elasticity to the skin. Under electron microscope, collagen fibers appears as of bundles of periodically banded fibrils which are composed of collagens types I, III and V; type V collagen is believed to assist in regulating fibril diameter. They are associated with FACITs (fibril-associated collagen with interrupted triple helixes) collagens types XIV et XVI. Collagen fibers provide tensile strength to the skin.
Non fibrous connective tissue molecules include finely filamentous glycoproteins, glycosaminoglycans and proteoglycans of "the ground substance" (hyaluronic acid and chondroitin sulphate, dermatan sulphate, versican, decorin). Fibroblasts, macrophages and mast cells are regular residents of the dermis. The main function of these cells are well known. Fibroblasts are responsible for the synthesis and the degradation of fibrous and non fibrous connective tissue matrix proteins. Macrophages are phagocytic; they process and present antigen to immunocompetent lymphoid cells. Mast cells are responsible for IgE mediated acute, subacute and chronic inflammation. All these cells have a long list of other functions, in particular they are involved in coagulation, wound healing and tissue remodeling.
The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on back and joint pain and skin impedance.
J Bone Miner Metab. 2002;20(5):298-302. Fujita T, Ohue M, Fujii Y, Miyauchi A, Takagi Y.
Katsuragi Hospital, 250 Makami-cho, Kishiwada, Osaka 596-0842, Japan.
The effect of active absorbable algal calcium (AAA Ca) with collagen and other matrix components on aging-associated skin changes and backache and joint pain was tested in a case-controlled study of 40 test subjects and 40 age-matched control subjects (mean age, 65 years) complaining of backache and knee joint pain due to osteoarthritis, spondylosis deformans, and/or osteoporosis. Supplementation with 900 mg calcium (given as AAA Ca) and 3.5 g collagen and other matrix components, including glucosamine, daily for 4 months resulted in a marked alleviation of subjective pain, assessed by the face scale. A fall of skin impedance in response to exercise loads, such as standing up, walking, squatting, and climbing up and down stairs, reported as an objective manifestion of pain, was also alleviated. The basal skin impedance, which increases with age, was significantly reduced in response to the Ca-collagen-matrix supplementation, suggesting a change of skin properties similar to rejuvenation, along with subjective smoothening and moistening of the skin. Urinary excretion of N-terminal crosslinking telopeptide of type I collagen (NTx) was decreased in the Ca-collagen-matrix supplementation group, but not in the control group. In addition to calcium suppression of parathyroid hormone, preventing bone resorption, collagen, acting on the intestinal lymphatic system, may protect collagen from degradation through the inhibition of cytokine-induced release of metalloproteinases, including collagenase.
Epidermis
Protective functions of epidermis
The primary function of the epidermis is to produce the protective, semi-permeable stratum corneum that permits terrestrial life. The barrier function of the stratum corneum is provided by patterned lipid lamellaelocalized to the extracellular spaces between corneocytes. Anucleate corneocytes contain keratin filamentsbound to a peripheral cornified envelope composed of cross-linked proteins. The many layers of these specialized cells in the stratum corneum provide a tough andresilient framework for the intercellular lipid lamellae.The lamellae are derived from disk-like lipid membranes extruded from lamellar granules into the intercellular spaces of the upper granular layer.
Lysosomal and other enzymes present in the extracellular compartment are responsible for the lipid remodeling required to generate the barrier lamellae as well as for the reactions that result in desquamation. Lamellar granules likely originate from the Golgi apparatus and are currently thought to be elements of the tubulo-vesicular trans-Golgi network. The regulation of barrier lipid synthesis has been studied in a variety of models, with induction of several enzymes demonstrated during fetal development and keratinocyte di¡erentiation, but an understanding of this process at the molecular genetic level awaits further study. Certain genetic defects in lipid metabolism or in the protein components of the stratum corneum produce scaly or ichthyotic skin with abnormal barrier lipid structure and function.
The inflammatory skin diseases psoriasis and atopic dermatitis also show decreased barrier function, but the underlying mechanisms remain under investigation. Topically applied ‘‘moisturizers’’ work by acting as humectants or by providing an artificial barrier to trans-epidermal water loss; current work has focused on developing a more physiologic mix of lipids for topical application to skin. Recent studies in genetically engineered mice have suggested an unexpected role for tight junctions in epidermal barrier function and further developments in this area are expected. Ultimately, more sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired.
Studies:
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