Two N-terminal ends of human type XVIII collagen chains have recently been identified. The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues , respectively, but share 301 residues of their NC1 domains as well as the collagenous and C-terminal noncollagenous portions of the molecule. Antibodies were produced against the NC1 region common to both human ␣1(XVIII) chain variants and against NC1 sequences specific to the long variant and were used in combination with in situ hybridization to localize this collagen in a number of human tissues. They were also used for Western blotting , which resulted in detection of overlapping high-molecular weight bands above the 200-kd standard in a kidney extract. Heparin lyase II and heparin lyase III digestions of kidney and placenta extracts indicated that at least in these tissues, type XVIII collagen contains heparin sulfate glycosaminoglycan side chains. Type XVIII collagen was found to be a ubiquitous basement membrane component , occurring prominently at vascular and epithelial basement membranes throughout the body. Comparison of the expression of the NC1-493 and NC1-303 variants revealed marked differences. The short variant was found in most conventional basement membranes , including blood vessels and the various epithelial structures , and around muscular structures. The long variant was expressed very strongly in liver , where it was virtually the only variant in the liver sinusoids , and it occurred only in minor amounts elsewhere. Thus , the 192 N-terminal residues specific to the long variant apparently confer some functional property needed above all in the liver sinusoids , but also at certain other locations. (Am J Pathol 1998, 153:611-626) Type XVIII collagen is an extracellular matrix protein recently identified by cDNA cloning.1-4 Elucidation of the complete mouse chain revealed it to be homologous with the previously identified type XV collagen, 5-7 and it has been suggested that type XV and XVIII collagens together form a subgroup of MULTIPLEXINs (multiple triple-helix domains with interruptions) within the collagen family.2 The mouse type XVIII collagen differs strikingly from type XV by the presence of variant polypeptide forms characterized by three N-terminal noncollagenous domains of differing lengths. 8,9 Interestingly, the longest ␣1(XVIII) chain form has a motif of 10 cysteine residues homologous to the extracellular part of the frizzled receptors involved in the Wingless signaling pathway in Drosophila. 10We have recently reported also the full-length human type XVIII collagen cDNAs that encode 1516-or 1336-amino acid residue ␣1(XVIII) chains. 11 The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share the last 301 residues of their NC1 domains, a 688-residue collagenous sequence (COL1 to COL10) with nine interruptions (NC2 to NC10), ...
Smoking decreases the synthesis rates of type I and III collagens in skin in vivo and alters the balance of extracellular matrix turnover in skin.
SUMMARYWe examined the expression of laminin-5 and its integrin receptors during reepithelialization of human wounds. We used suction blisters of skin as a model of keratinocyte migration on a basement membrane matrix and mucosal full-thickness wounds as a model in which keratinocytes migrate in a provisional matrix. An animal model, in which human epidermal keratinocytes were injected into the back of athymic mice, was used to follow the deposition of the basement membrane components. In 4-day-old blisters, about 20-50 cells at the leading edge of the migrating tongue showed cytoplasmic laminin-5 immunostaining. Laminin-5 mRNA was detected in 15-30 cells at the leading edge of the migrating epidermis. ␣ 3  1 and ␣ 6  4 integrins were found in membrane projections of the migrating basal cells and also in suprabasal cell layers, suggesting their combined role in binding laminin-5. In mucosal wounds, laminin-5 was the only basement membrane zone component that was deposited between the clot and the migrating keratinocytes. In the animal model, linear deposition of laminin-5 and ␣ 6  4 integrin was already seen on Day 2, whereas the other basement membrane zone components were not yet organized. The results suggest that, regardless of the injury and the microenvironment, laminin-5 plays an essential role in the interaction between wound keratinocytes and the surrounding matrix.
Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis and several matrix metalloproteinases have previously been implicated in this process. Using immunohistochemistry and in situ hybridization, we have studied the localization of two elastolytic matrix metalloproteinases, matrilysin (matrix metalloproteinase-7) and human macrophage metalloelastase (matrix metalloproteinase-12) in solar damage. Human macrophage metalloelastase protein was detected in the superficial dermis in areas of elastotic material. Matrix metalloproteinase-7 was seen in the mid-dermis in regions with less damaged elastic fibers and morphologically better preserved collagen as well as in a band-like pattern below basal keratinocytes in eight of 18 solar elastosis. In samples taken from healthy volunteers 3 d after repeated ultraviolet A or ultraviolet B photoprovocation, occasional immunopositive cells for human macrophage metalloelastase (stromal) or matrix metalloproteinase-7 (sweat gland epithelium) were detected. In samples taken 1 d after ultraviolet B exposure, however, basal keratinocytes were matrix metalloproteinase-7 immunopositive, explaining the linear immunostaining below basal keratinocytes noted particularly in ultraviolet B treated 3 d specimens. Upregulation of metalloelastase was also demonstrated in the skin of hairless mice after repeated ultraviolet exposure. In normal skin, no staining for human macrophage metalloelastase or matrix metalloproteinase-7 was observed in association with elastin. The amount of immunoreactivity for the substrates of matrix metalloproteinase-7, versican, and tenascin, was clearly increased in solar elastosis and photoprovocated skin; versican but not tenascin was detected in the same areas as matrix metalloproteinase-7. Our results suggest that both matrix metalloproteinase-7 and -12 may contribute to remodeling of elastotic areas in sun-damaged skin.
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