Altered expression of basement membrane proteins and their integrin receptors in lichen planus: possible pathogenetic role of gelatinases A and B.

Giannelli G, Brassard J, Foti C, Stetler-Stevenson WG, Falk-Marzillier J, Zambonin-Zallone A, Schiraldi O, Quaranta V
Lab Invest. 1996 74 (6): 1091-104

PMID: 8667613

Lichenoid lesions of the skin are characterized by a band-like dermal inflammatory infiltrate and structural alterations of the basement membrane (BM). The etiopathogenesis of these lesions, of which lichen planus (LP) is perhaps the prototypic example, is unknown. Acute cases of LP are accompanied by the destruction of epidermal BM, degeneration of basal keratinocytes with loss of tonofilaments and hemidesmosomes, vesicular alterations, and even blister formation. Chronic LP is characterized by hyperkeratosis and acanthosis in the epidermis, fibrosis, and dense infiltrate in dermis. We found that acute LP lesions are characterized by uneven or absent immunostaining for laminin-5, laminin-1, and collagen type IV. Distribution and activity of gelatinases matrix metalloproteinase (MMP)-9 and MMP-2, and a specific inhibitor of MMP-2, tissue inhibitor of metalloprotein-2, were analyzed. The expression and activity of MMP-2 were increased, whereas tissue inhibitor of metalloprotein-2 expression was weak in the involved areas during the acute phase of LP. Moreover, we demonstrated in vitro that MMP-2 is directly capable of digesting laminin-5 gamma 2 chains to yield a 80-kd fragment. We also observed a weak or absent staining of all examined integrin receptors in the acute LP lesions. In chronic lesions, the staining of BM components was similar to normal controls. In these sections, normal expression of gelatinases and inhibitor was observed. There was, however, up-regulation and altered polarity of integrin receptors. These results indicate a link between overexpression of gelatinases, BM disruption, and altered integrin expression. In LP, the digestion of BM by MMP-2 may contribute to the pathogenesis by inducing altered integrin expression in basal keratinocytes and ultimately blister formation.

MeSH Terms (24)

Adolescent Adult Aged Basement Membrane Cell Adhesion Molecules Cell Division Collagenases Electrophoresis, Polyacrylamide Gel Epidermis Extracellular Matrix Proteins Female Gelatinases Humans Integrins Keratinocytes Lichen Planus Male Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Metalloendopeptidases Middle Aged Mouth Mucosa Protein Biosynthesis Tissue Inhibitor of Metalloproteinase-2

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