title: Collagenase 3 (matrix metalloproteinase 13) gene expression by HaCaT keratinocytes is enhanced by tumor necrosis factor alpha and transforming growth factor beta.
abstract: Collagenase-3 (matrix metalloproteinase 13; MMP-13) is a novel matrix metalloproteinase, the expression of which to date has only been detected in human breast carcinoma tissue and osteoarthritic cartilage. Here, we show that MMP-13 transcripts are expressed by human HaCaT keratinocytes but not by primary human epidermal keratinocytes. The levels of MMP-13 mRNAs in HaCaT cells were enhanced up to 130- and 45-fold by tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), respectively. The maximal induction of MMP-13 mRNAs by TNF-alpha was noted after a 6-h incubation, whereas with TGF-beta, the maximal stimulation was observed after 24 h. The up-regulation of MMP-13 mRNA abundance by TNF-alpha and TGF-beta was dependent on protein synthesis and was prevented partially by dexamethasone and retinoic acid. Nuclear run-on assays demonstrated activation of MMP-13 gene transcription by TNF-alpha maximally at the 2-h time point and by TGF-beta after 12 h of treatment. Incubation of HaCaT keratinocytes with TNF-alpha and TGF-beta also increased production of proMMP-13 into the culture media, as detected by Western blotting. Our data indicate that the MMP-13 gene is expressed by transformed epidermal keratinocytes, suggesting a role for MMP-13 in the invasive capacity of human epidermal malignancies.
authors.affiliation: Department of Dermatology, Turku University Central Hospital, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Johansson
authors.forename: J
authors.initials: J
authors.lastname: Westermarck
authors.forename: S
authors.initials: S
authors.lastname: Leppä
authors.forename: L
authors.initials: L
authors.lastname: Häkkinen
authors.forename: L
authors.initials: L
authors.lastname: Koivisto
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
authors.forename: J
authors.initials: J
authors.lastname: Peltonen
authors.forename: J
authors.initials: J
authors.lastname: Heino
authors.forename: V M
authors.initials: VM
authors.lastname: Kähäri
mesh_terms: D015152:Blotting, Northern; D002460:Cell Line; D002461:Cell Line, Transformed / Q000187:drug effects / Q000502:physiology; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D053509:Matrix Metalloproteinase 13; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D003907:Dexamethasone; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13