title: Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage.
abstract: 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.
authors.affiliation: Department of Dermatology, Helsinki University Central Hospital, Finland. ulpu.saarialho-kere@helsinki.fi
authors.forename: U
authors.initials: U
authors.lastname: Saarialho-Kere
authors.forename: E
authors.initials: E
authors.lastname: Kerkelä
authors.forename: L
authors.initials: L
authors.lastname: Jeskanen
authors.forename: T
authors.initials: T
authors.lastname: Hasan
authors.forename: R
authors.initials: R
authors.lastname: Pierce
authors.forename: B
authors.initials: B
authors.lastname: Starcher
authors.forename: R
authors.initials: R
authors.lastname: Raudasoja
authors.forename: A
authors.initials: A
authors.lastname: Ranki
authors.forename: A
authors.initials: A
authors.lastname: Oikarinen
authors.forename: M
authors.initials: M
authors.lastname: Vaalamo
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis; D004549:Elastin / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007642:Keratosis / Q000201:enzymology; D037181:Lectins, C-Type; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008812:Mice, Hairless; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects*; D019063:Tenascin / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000502:physiology; D014466:Ultraviolet Rays / Q000009:adverse effects; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D012333:RNA, Messenger; D019063:Tenascin; D016212:Transforming Growth Factor beta; C508322:VCAN protein, human; C508323:Vcan protein, mouse; D053675:Versicans; D004549:Elastin; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12