Matrix metalloproteinase-19 expression in keratinocytes is repressed by transcription factors Tst-1 and Skn-1a: implications for keratinocyte differentiation.
Matrix metalloproteinase-19 (MMP-19), unlike other members of the MMP family, is expressed in basal keratinocytes of intact epidermis whereas keratinocytes in suprabasal and higher epidermal layers express this enzyme only during cutaneous disorders. As the activity of MMP-19 effects proliferation, migration, and adhesion of keratinocytes we examined whether transcription factors involved in keratinocyte differentiation repress the expression of MMP-19. Using luciferase reporter assays, POU transcription factors Tst-1 (Oct-6) and Skn-1a (Oct-11) markedly downregulated the activity of MMP-19 promoter in COS-7 cells and HaCaT keratinocytes. Tst-1 alone was able to inhibit 85% of the promoter activity. Skn-1a exhibited a weak inhibitory effect although it synergistically increased effects of Tst-1. HaCaT cells stably transfected with Tst-1 showed a strong decrease of activity of MMP-19 promoter that correlated with suppression of MMP-19, cytokeratin 14 and 5, decreased cell proliferation, and altered expression of involucrin and loricrin. The expression of MMP-9 was also significantly reduced in Tst-1 expressing keratinocytes. MMP-2 was substantially affected during its activation whereas the expression of MMP-28 was unchanged. Our results suggest that Tst-1 and Skn-1a regulate expression of MMPs in keratinocytes and effect both the expression and activation of these proteolytic enzymes.
Beck
Inken M
IM
Institute of Biochemistry, University of Kiel, Kiel, Germany.
Müller
Matthias
M
Mentlein
Rolf
R
Sadowski
Thorsten
T
Mueller
Markus S
MS
Paus
Ralf
R
Sedlacek
Radislav
R
D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D006801:Humans; D053547:Keratin-14 / Q000235:genetics / Q000502:physiology; D053555:Keratin-5 / Q000235:genetics / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology; D053505:Matrix Metalloproteinases, Secreted; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000502:physiology*; D050810:Octamer Transcription Factors / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics / Q000502:physiology
D053547:Keratin-14; D053555:Keratin-5; D008565:Membrane Proteins; D050810:Octamer Transcription Factors; C484169:POU2F3 protein, human; D011498:Protein Precursors; C064554:loricrin; D050816:Octamer Transcription Factor-6; C032253:involucrin; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9