Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2

Raul Fleischmajer, Kei Kuroda, Rachel Hazan, Ronald E. Gordon, Mark G. Lebwohl, Allen N. Sapadin, Fernando Unda, Noriyuki Iehara, Yoshihiko Yamada

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)771-777
Number of pages7
JournalJournal of Investigative Dermatology
Volume115
Issue number5
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Psoriasis
Basement Membrane
Tissue
Keratinocytes
Skin
Epidermis
Cell-Matrix Junctions
Tissue Inhibitor of Metalloproteinase-2
Cell proliferation
Laminin
Gelatin
Matrix Metalloproteinases
In Situ Hybridization
Cytoplasm
Collagen
Adhesion
Western Blotting
Immunohistochemistry

Keywords

  • Cell adhesion
  • MMP-2
  • Psoriasis
  • TIMP-2

ASJC Scopus subject areas

  • Dermatology

Cite this

Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2. / Fleischmajer, Raul; Kuroda, Kei; Hazan, Rachel; Gordon, Ronald E.; Lebwohl, Mark G.; Sapadin, Allen N.; Unda, Fernando; Iehara, Noriyuki; Yamada, Yoshihiko.

In: Journal of Investigative Dermatology, Vol. 115, No. 5, 2000, p. 771-777.

Research output: Contribution to journalArticle

Fleischmajer, Raul ; Kuroda, Kei ; Hazan, Rachel ; Gordon, Ronald E. ; Lebwohl, Mark G. ; Sapadin, Allen N. ; Unda, Fernando ; Iehara, Noriyuki ; Yamada, Yoshihiko. / Basement membrane alterations in psoriasis are accompanied by epidermal overexpression of MMP-2 and its inhibitor TIMP-2. In: Journal of Investigative Dermatology. 2000 ; Vol. 115, No. 5. pp. 771-777.
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abstract = "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.",
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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

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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.

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