TY - JOUR
T1 - Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2
AU - Fleischmajer, Raul
AU - Kuroda, Kei
AU - Hazan, Rachel
AU - Gordon, Ronald E.
AU - Lebwohl, Mark G.
AU - Sapadin, Allen N.
AU - Unda, Fernando
AU - Iehara, Noriyuki
AU - Yamada, Yoshihiko
PY - 2000
Y1 - 2000
N2 - Psoriasis is most probably an inherited disease characterized by cell proliferation, angiogenesis, and an inflammatory process. The pathophysiology remains unknown, although an alteration in cell-cell and cell-matrix adhesion versus an autoimmune process has been proposed as the primary defect. Here, we show evidence of a new mechanism involving basement membrane alterations accompanied by keratinocyte overexpression of matrix metalloproteinase (MMP) 2 and tissue inhibitor of MMP-2 (TIMP-2) in both uninvolved and involved psoriatic skin. Immunocytochemistry with antibodies against collagen IV (α1, α2 chains) and laminins (α2, α5, β1, γ1 chains) revealed gaps, folding, and reduplication of the epidermo-dermal basement membrane. There was overexpression of MMP-2 in the cytoplasm of suprabasal keratinocytes. Gelatin zymography revealed pro-MMP-2 and its activated form, a-MMP-2, in both uninvolved and involved psoriatic skin, whereas pro-MMP-9 was only present in involved skin. TIMP-2 was expressed at the cell surface of psoriatic involved suprabasal keratinocytes whereas it was restricted to basal keratinocytes in uninvolved areas. Western blots showed a marked increase in a-MMP-2 and TIMP-2 in uninvolved and involved psoriatic skin although it was more pronounced in the latter. MT1-MP, known to activate pro-MMP-2, was increased in involved areas. In situ hybridization revealed strong signals of MMP-2 mRNA in both uninvolved and involved psoriatic epidermis. The overexpression of MMP-2 in uninvolved and involved psoriatic epidermis supports the concept that the primary alteration may reside in the keratinocyte. In addition, the presence of the activated form of MMP-2 could be responsible for cell-cell and cell-matrix changes noted in psoriatic epidermis.
AB - Psoriasis is most probably an inherited disease characterized by cell proliferation, angiogenesis, and an inflammatory process. The pathophysiology remains unknown, although an alteration in cell-cell and cell-matrix adhesion versus an autoimmune process has been proposed as the primary defect. Here, we show evidence of a new mechanism involving basement membrane alterations accompanied by keratinocyte overexpression of matrix metalloproteinase (MMP) 2 and tissue inhibitor of MMP-2 (TIMP-2) in both uninvolved and involved psoriatic skin. Immunocytochemistry with antibodies against collagen IV (α1, α2 chains) and laminins (α2, α5, β1, γ1 chains) revealed gaps, folding, and reduplication of the epidermo-dermal basement membrane. There was overexpression of MMP-2 in the cytoplasm of suprabasal keratinocytes. Gelatin zymography revealed pro-MMP-2 and its activated form, a-MMP-2, in both uninvolved and involved psoriatic skin, whereas pro-MMP-9 was only present in involved skin. TIMP-2 was expressed at the cell surface of psoriatic involved suprabasal keratinocytes whereas it was restricted to basal keratinocytes in uninvolved areas. Western blots showed a marked increase in a-MMP-2 and TIMP-2 in uninvolved and involved psoriatic skin although it was more pronounced in the latter. MT1-MP, known to activate pro-MMP-2, was increased in involved areas. In situ hybridization revealed strong signals of MMP-2 mRNA in both uninvolved and involved psoriatic epidermis. The overexpression of MMP-2 in uninvolved and involved psoriatic epidermis supports the concept that the primary alteration may reside in the keratinocyte. In addition, the presence of the activated form of MMP-2 could be responsible for cell-cell and cell-matrix changes noted in psoriatic epidermis.
KW - Cell adhesion
KW - MMP-2
KW - Psoriasis
KW - TIMP-2
UR - http://www.scopus.com/inward/record.url?scp=0033748378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033748378&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1747.2000.00138.x
DO - 10.1046/j.1523-1747.2000.00138.x
M3 - Article
C2 - 11069613
AN - SCOPUS:0033748378
SN - 0022-202X
VL - 115
SP - 771
EP - 777
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -