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A Positive Loop Formed by SOX11 and Periostin Upregulates TGF-ß Signals Leading to Skin Fibrosis.
Nanri, Yasuhiro; Nunomura, Satoshi; Honda, Yuko; Takedomi, Hironobu; Yamaguchi, Yukie; Izuhara, Kenji.
Afiliación
  • Nanri Y; Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
  • Nunomura S; Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
  • Honda Y; Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
  • Takedomi H; Department of Internal Medicine, Saga Medical School, Saga, Japan.
  • Yamaguchi Y; Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Izuhara K; Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan. Electronic address: kizuhara@cc.saga-u.ac.jp.
J Invest Dermatol ; 143(6): 989-998.e7, 2023 06.
Article en En | MEDLINE | ID: mdl-36584910
Systemic sclerosis (SSc) is a chronic, heterogeneous disease of connective tissue characterized by organ fibrosis together with vascular injury and autoimmunity. TGF-ß plays a central role in generating fibrosis, including SSc. Periostin is a matricellular protein playing a key role in the generation of fibrosis by amplifying the TGF-ß signals. SOX11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that SOX11 induces periostin expression. However, the roles of the interactions among the TGF-ß signals, periostin, and SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that most clones of dermal fibroblasts derived from patients with SSc showed constitutive, high expression of SOX11, which is significantly induced by TGF-ß1. SOX11 forms a positive loop with periostin to activate the TGF-ß signals in SSc dermal fibroblasts. Genetic deletion of Sox11 in Postn-expressing fibroblasts impairs dermal fibrosis by bleomycin. Moreover, using the DNA microarray method, we identified several fibrotic factors dependent on the TGF-ß/SOX11/periostin pathway in SSc dermal fibroblasts. Our findings, taken together, show that a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF-ß signals, leading to skin fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Factor de Crecimiento Transformador beta Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerodermia Sistémica / Factor de Crecimiento Transformador beta Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos