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Antifibrotic effect of apremilast in systemic sclerosis dermal fibroblasts and bleomycin-induced mouse model.
Higuchi, Tomoaki; Takagi, Kae; Tochimoto, Akiko; Ichimura, Yuki; Hirose, Hikaru; Sawada, Tatsuo; Shibata, Noriyuki; Harigai, Masayoshi; Kawaguchi, Yasushi.
Afiliación
  • Higuchi T; Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. higuchi.tomoaki@twmu.ac.jp.
  • Takagi K; Division of Multidisciplinary Management of Rheumatic Diseases, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. higuchi.tomoaki@twmu.ac.jp.
  • Tochimoto A; Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
  • Ichimura Y; Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
  • Hirose H; Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
  • Sawada T; Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • Shibata N; Division of Rheumatology, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
  • Harigai M; Department of Pathology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
  • Kawaguchi Y; Department of Pathology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Sci Rep ; 13(1): 19378, 2023 11 08.
Article en En | MEDLINE | ID: mdl-37938601
Phosphodiesterase (PDE) 4 inhibitors have been reported to suppress the progression of dermal fibrosis in patients with systemic sclerosis (SSc); however, the precise mechanisms remain to be elucidated. Therefore, we conducted experiments focusing on the antifibrotic and anti-inflammatory effects of apremilast using dermal fibroblasts derived from patients with SSc and an SSc mouse model. Dermal fibroblasts derived from healthy controls and patients with SSc were incubated with apremilast in the presence or absence of 10 ng/ml transforming growth factor (TGF)-ß1 for the measurement of intracellular cAMP levels and evaluation of mRNA and protein expression. A bleomycin-induced dermal fibrosis mouse model was used to evaluate the inhibitory effects of apremilast on the progression of dermal fibrosis. Intracellular cAMP levels were significantly reduced in dermal fibroblasts derived from patients with SSc compared with those derived from healthy controls. Apremilast reduced the mRNA expression of profibrotic markers and the protein expression of type I collagen and Cellular Communication Network Factor 2 (CCN2) in dermal fibroblasts. Additionally, apremilast inhibited the progression of dermal fibrosis in mice, partly by acting on T cells. These results suggest that apremilast may be a potential candidate for treating dermal fibrosis in SSc.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Inhibidores de Fosfodiesterasa 4 Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Inhibidores de Fosfodiesterasa 4 Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido