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Matrix metalloproteinase-19 expression in normal and diseased skin: dysregulation by epidermal proliferation
Thorsten Sadowski1, Sebastian Dietrich, Matthias Müller
1Institute of Biochemistry, University of Kiel, Kiel, Germany.
Abstract:
Most of the matrix metalloproteinases (MMP) are not expressed in normal intact skin but they are upregulated in inflamed or diseased skin. The recently cloned MMP-19 is one of the few MMP members that are also expressed in healthy epidermis. In this study, we found that MMP-19 is generally coexpressed with cytokeratin 14 that is confined to keratinocytes of the stratum basale. MMP-19 was also detected in hair follicles, sebaceous glands, and eccrine sweat glands. Its expression, however, changed in cutaneous diseases exhibiting increased alternations of epidermal proliferation, such as psoriasis, eczema, and tinea. In the affected area, MMP-19 was also found in suprabasal and spinous epidermal layers. We also studied the regulation of MMP-19 expression at the protein level, as well as by using a promoter assay. The constitutive expression of MMP-19 was upregulated with phorbol myristate acetate and downregulated with retinoic acid and dexamethasone. Tumor necrosis factor-alpha, interleukin (IL)-6, TGF-beta, IL-15, IL-8, and RANTES as well as the bacterial compounds lipopolysaccharide and lipoteichoic acid did not show any profound effect in HaCaT cells. In contrast, type IV and type I collagens upregulated MMP-19 significantly. The dysregulation of MMP-19 expression in epidermis suggests its possible involvement in the perpetuation of cutaneous infections and proliferative disorders such as psoriasis.
Insights
Matrix metalloproteinase-19 (MMP-19) is expressed in healthy skin and its levels change in skin diseases. Dysregulation of MMP-19 in the epidermis may contribute to skin infections and proliferative disorders like psoriasis.
Area of Science:
- Dermatology
- Molecular Biology
- Biochemistry
Background:
- Most matrix metalloproteinases (MMPs) are upregulated in diseased skin, but MMP-19 is also expressed in healthy epidermis.
- MMP-19 is coexpressed with cytokeratin 14 in the basal layer of the epidermis and found in skin appendages.
Purpose of the Study:
- To investigate the expression pattern of MMP-19 in healthy and diseased skin.
- To explore the regulatory mechanisms of MMP-19 expression at the protein and promoter levels.
Main Methods:
- Immunohistochemistry to detect MMP-19 expression in skin tissues.
- Promoter assays and Western blotting to study MMP-19 regulation in HaCaT cells.
- Treatment of cells with various agents including phorbol myristate acetate, retinoic acid, dexamethasone, cytokines, bacterial compounds, and collagens.
Main Results:
- MMP-19 expression was observed in healthy epidermis, hair follicles, sebaceous glands, and eccrine sweat glands.
- Expression levels and localization of MMP-19 changed in skin diseases like psoriasis, eczema, and tinea, with increased presence in suprabasal and spinous layers.
- Phorbol myristate acetate upregulated MMP-19, while retinoic acid and dexamethasone downregulated it. Type I and IV collagens significantly upregulated MMP-19 in HaCaT cells. Cytokines and bacterial compounds had minimal effects.
Conclusions:
- MMP-19 exhibits constitutive expression in healthy skin and is dysregulated in various cutaneous diseases.
- The findings suggest MMP-19's potential role in the pathogenesis of skin infections and proliferative disorders, including psoriasis.
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