title: Demonstration of 72-kDa and 92-kDa forms of type IV collagenase in human skin: variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids.
abstract: Type IV collagenases have been shown to play an important role in tumor metastasis and wound healing. In the present study, we have demonstrated the presence of 72-kDa and 92-kDa forms of type IV collagenase in human skin by biochemical and in situ hybridization techniques. In situ hybridization allowed us to localize the 72-kDa form mostly to fibroblasts and the 92-kDa form to the epidermis and endothelial cells. The presence of type IV collagenase was confirmed by Western blotting. Enzyme activity was assayed in spontaneous blisters (18 subjects) and suction-induced blisters (29 subjects) by the zymography method, and by using type IV collagen as the substrate. Thus, it was possible to detect both the 92-kDa and 72-kDa forms in spontaneous and induced blisters. An especially high level of the 92-kDa enzyme was found in a bullous pemphigoid patient. Type IV collagenases were studied during re-epithelialization of the blister, using the suction-blister model. There was a marked induction of the 92-kDa type that was confirmed to be in the regenerating, migratory, epithelium by in situ hybridization studies. These results indicate that 92-kDa type IV collagenase may play an essential role in the normal physiology and integrity of the skin and may be an important regulator of re-epithelialization. It was also shown that potent topical glucocorticoid down-regulated the 92-kDa type collagenase, suggesting that glucocorticoids may have a beneficial role in some skin diseases by decreasing type IV collagenase activity and, thus, reducing tissue destruction.
authors.affiliation: Department of Dermatology, University of Oulu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Oikarinen
authors.forename: M
authors.initials: M
authors.lastname: Kylmäniemi
authors.forename: H
authors.initials: H
authors.lastname: Autio-Harmainen
authors.forename: P
authors.initials: P
authors.lastname: Autio
authors.forename: T
authors.initials: T
authors.lastname: Salo
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017364:Collagenases / Q000032:analysis* / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D004790:Enzyme Induction; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D005938:Glucocorticoids; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000032:analysis* / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D012872:Skin Diseases, Vesiculobullous / Q000201:enzymology*; D014212:Tretinoin / Q000494:pharmacology; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D014212:Tretinoin; D017364:Collagenases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9