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Mithramycin has inhibitory effects on gliostatin and matrix metalloproteinase expression induced by gliostatin in rheumatoid fibroblast-like synoviocytes.
Tatematsu, Naoe; Waguri-Nagaya, Yuko; Kawaguchi, Yohei; Oguri, Yusuke; Ikuta, Kenji; Kobayashi, Masaaki; Nozaki, Masahiro; Asai, Kiyofumi; Aoyama, Mineyoshi; Otsuka, Takanobu.
Afiliação
  • Tatematsu N; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Waguri-Nagaya Y; b Department of Joint Surgery for Rheumatic Diseases , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Kawaguchi Y; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Oguri Y; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Ikuta K; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Kobayashi M; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Nozaki M; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Asai K; c Department of Molecular Neurobiology , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
  • Aoyama M; d Department of Pathobiology , Nagoya City University Graduate School of Pharmaceutical Sciences , Nagoya , Japan.
  • Otsuka T; a Department of Orthopaedic Surgery , Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan.
Mod Rheumatol ; 28(3): 495-505, 2018 May.
Article em En | MEDLINE | ID: mdl-28741989
ABSTRACT

OBJECTIVES:

Gliostatin (GLS) has angiogenic and arthritogenic activities and enzymatic activity as thymidine phosphorylase. Aberrant GLS production has been observed in the synovial membranes of patients with rheumatoid arthritis (RA). Matrix metalloproteinases (MMPs) are involved in joint destruction. Promoters of GLS and some MMP genes contain Sp1 binding sites. We examined the inhibitory effect of the Sp1 inhibitor mithramycin on GLS-induced GLS and MMP expression in cultured fibroblast-like synoviocytes (FLSs).

METHODS:

Synovial tissue samples were obtained from patients with RA. FLSs pretreated with mithramycin were cultured with GLS. The mRNA expression levels of GLS and MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13 were determined using reverse transcription polymerase chain reactions. Protein levels were measured using enzyme immunoassay and gelatin zymography.

RESULTS:

GLS upregulated the expression of GLS itself and of MMP-1, MMP-3, MMP-9, and MMP-13, an effect significantly reduced by treatment with mithramycin. GLS and mithramycin had no effect on MMP-2 expression.

CONCLUSIONS:

Mithramycin downregulated the increased expression of GLS and MMP-1, MMP-3, MMP-9, and MMP-13 in FLSs treated with GLS. Because GLS plays a pathological role in RA, blocking GLS stimulation using an agent such as mithramycin may be a novel approach to antirheumatic therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Timidina Fosforilase / Plicamicina / Metaloproteinases da Matriz / Sinoviócitos Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mod Rheumatol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Timidina Fosforilase / Plicamicina / Metaloproteinases da Matriz / Sinoviócitos Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Mod Rheumatol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Japão