Matrix metalloproteinase-21 expression is associated with keratinocyte differentiation and upregulated by retinoic acid in HaCaT cells.
Skoog T, Elomaa O, Pasonen-Seppanen SM et al. J Invest Dermatol, 2009, 129, 119-130
Matrix metalloproteinase-21 (MMP) is a recently cloned member of the MMP family. In skin, expression of MMPs occurs in response to tissue injury and inflammation. It is different from other MMPs in that it is not upregulated in keratinocytes as a response to tissue injury and to date, only among cytokines and growth factors, TGF-[beta]1 induces mRNA expression in keratinocytes. Retinoid receptor binding sites have been identified in the promoter region for MMP-21 expression, thus retinoic acid upregulates MMP21 mRNA in monocytic U937 cells  and the enzyme has been found in cancer cells. This work further investigated the role of MMP-21 in keratinocyte function using cells isolated from skin biopsies as well as cultured keratinocyte cell lines such as HaCaT cells.
In HaCaT cells, [10.sup.-6] and [10.sup.-7]M retinoic acid (RA) induced an upregulation of MMP-21 by 2.2-fold mRNA and protein, but this was not associated with cell proliferation or apoptosis. In fact, the RA-induced increase of MMP-21 was linked to keratinocyte differentiation in normal and diseased epidermis. Along with the response to RA, there was an associated increase in levels of involucrin and filaggrin at the protein level as demonstrated with immunofluorescent labelling. Expression of MMP-21 was studied in several skin diseases by obtaining biopsies of the relevant condition. MMP-21 was expressed in actinic keratosis, Bowen's disease, pyoderma gangrenosum, lichen planus and all keratoacanthomas studied in the keratinocytes of the upper spiny layers of epidermis. These cells were frequently also spongiotic and lacked normal E-cadherin staining. Functionally, MMP-21 was not demonstrated to be involved in cellular migration but influenced adhesion to type VI collagen and increased invasion of cells.
In summary, the authors conclude that MMP-21 is expressed by suprabasal keratinocytes in certain benign disorders and is induced in differentiating keratinocytes, thus it may be an important protease in this process.
[1.] Skoog T, Ahokas K, Orsmark C et al, MMP-21 is expressed by macropahges and fibroblasts in vivo and in culture. Exp Dermatol, 2006, 15, 775-783.
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|Date:||Mar 1, 2009|
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