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Harmine suppresses collagen production in hepatic stellate cells by inhibiting DYRK1B.
Yamaguchi, Momoka; Ohbayashi, Saya; Ooka, Akira; Yamashita, Hinako; Motohashi, Nanami; Kaneko, Yukiko K; Kimura, Toshihide; Saito, Shin-Ya; Ishikawa, Tomohisa.
Afiliación
  • Yamaguchi M; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan. Electronic address: yamamomo@u-shizuoka-ken.ac.jp.
  • Ohbayashi S; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Ooka A; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Yamashita H; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Motohashi N; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Kaneko YK; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Kimura T; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
  • Saito SY; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan; Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoinooka, Imabari City, Ehime, 794-8555, Japan.
  • Ishikawa T; Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
Biochem Biophys Res Commun ; 600: 136-141, 2022 04 16.
Article en En | MEDLINE | ID: mdl-35219102
Liver fibrosis is a major consequence of chronic liver disease, where excess extracellular matrix is deposited, due caused by the activation of hepatic stellate cells (HSCs). The suppression of collagen production in HSCs is therefore regarded as a therapeutic target of liver fibrosis. The present study investigated effects of harmine, which is a ß-carboline alkaloid and known as an inhibitor of dual-specificity tyrosine-regulated kinases (DYRKs), on the production of collagen in HSCs. LX-2 cells, a human HSC cell line, were treated with harmine (0-10 µM) for 48 h in the presence or absence of TGF-ß1 (5 ng/ml). The expression of collagen type I α1 (COL1A1) and DYRK isoforms was investigated by Western blotting, quantitative RT-PCR, or immunofluorescence. The influence of knockdown of each DYRK isoform on the COL1A1 expression was further investigated. The expression of COL1A1 was markedly increased by treating with TGF-ß1 for 48 h in LX-2 cells. Harmine (10 µM) significantly inhibited the increased expression of COL1A1. LX-2 cells expressed mRNAs of DYRK1A, DYRK1B, DYRK2, and DYRK4, although the expression of DYRK4 was much lower than the others. Knockdown of DYRK1B, but not DYRK1A or DYRK2, with siRNA significantly suppressed TGF-ß1-induced increase in COL1A1 expression. These results suggest that harmine suppresses COL1A1 expression via inhibiting DYRK1B in HSCs and therefore might be effective for the treatment of liver fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Tirosina Quinasas / Proteínas Serina-Treonina Quinasas / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas / Cadena alfa 1 del Colágeno Tipo I / Harmina Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Tirosina Quinasas / Proteínas Serina-Treonina Quinasas / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas / Cadena alfa 1 del Colágeno Tipo I / Harmina Límite: Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos