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.
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.
Oikarinen
A
A
Department of Dermatology, University of Oulu, Finland.
Kylmäniemi
M
M
Autio-Harmainen
H
H
Autio
P
P
Salo
T
T
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*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D014212:Tretinoin; D017364:Collagenases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9