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 journalArticlepeer-review

51 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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