Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair.
Epilysin (MMP-28) is the newest member of the matrix metalloproteinase enzyme family. Several members of this enzyme family have been associated with various aspects of wound repair and cancer invasion. The aim of this study was to characterize in different types of wounds, skin cancers, and keratinocyte cultures factors that contribute to epilysin expression in vivo, as well as how and where it is induced in relation to other matrix metalloproteinases. Our results indicate that epilysin is produced by the mitotic Ki-67-positive keratinocytes distal from the wound edge in both acute and chronic wounds and that it does not generally colocalize with collagenase-1, stromelysin-2, or 92 kDa gelatinase in migrating keratinocytes. An injury of epidermis was needed for epilysin induction as it was upregulated in ulcerated pyogenic granulomas and in suction blisters but was not detected in intact acanthotic or normal skin. Unlike many other matrix metalloproteinases, epilysin was not detected in the invading cancer cell nests of sclerosing basal or squamous cell cancers of various grades. When primary keratinocytes were stimulated with tumor necrosis factor alpha, upregulation of epilysin mRNA was evident within 24-48 h as measured by quantitative reverse transcription polymerase chain reaction. In primary keratinocyte, HaCaT, and A431 carcinoma cell cultures none of the 10 other growth factors or extracellular matrices studied were able to upregulate epilysin expression. Our results suggest that epilysin expression is tightly spatially and temporally regulated during wound repair. Although the in vivo substrates of epilysin are not known at present, its expression pattern suggests that it may be needed to restructure the basement membrane or to degrade adhesive proteins between keratinocytes to supply new cells for the migrating front.
Saarialho-Kere
Ulpu
U
Department of Dermatology, Biomedicum Helsinki, University Central Hospital, University of Helsinki, Meilahdentie 2, 00250 Helsinki, Finland. ulpu.saarialho-kere@helsinki.fi
Kerkelä
Erja
E
Jahkola
Tiina
T
Suomela
Sari
S
Keski-Oja
Jorma
J
Lohi
Jouko
J
D001768:Blister / Q000473:pathology / Q000503:physiopathology; D002280:Basal Cell Carcinoma / Q000473:pathology / Q000503:physiopathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D019394:Ki-67 Antigen / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053505:Matrix Metalloproteinases, Secreted; D012333:RNA, Messenger / Q000032:analysis; D012878:Skin Neoplasms / Q000473:pathology / Q000503:physiopathology; D013396:Suction; D014945:Wound Healing / Q000502:physiology*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D019394:Ki-67 Antigen; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D012333:RNA, Messenger; D000097794:Kalinin; C424663:MMP28 protein, human