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Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds.
de Kerckhove, Maiko; Tanaka, Katsuya; Umehara, Takahiro; Okamoto, Momoko; Kanematsu, Sotaro; Hayashi, Hiroko; Yano, Hiroki; Nishiura, Soushi; Tooyama, Shiho; Matsubayashi, Yutaka; Komatsu, Toshimitsu; Park, Seongjoon; Okada, Yuka; Takahashi, Rina; Kawano, Yayoi; Hanawa, Takehisa; Iwasaki, Keisuke; Nozaki, Tadashige; Torigoe, Hidetaka; Ikematsu, Kazuya; Suzuki, Yutaka; Tanaka, Katsumi; Martin, Paul; Shimokawa, Isao; Mori, Ryoichi.
Afiliación
  • de Kerckhove M; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Tanaka K; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Umehara T; Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Okamoto M; Department of Plastic and Reconstructive Surgery, Ehime Prefectural Center Hospital, Ehime, Japan.
  • Kanematsu S; Department of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Hayashi H; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Yano H; Department of Immunology and Rheumatology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Nishiura S; Laboratory of Functional Genomics, Department of Medical Genome Science, Graduate of Frontier Science, The University of Tokyo, Tokyo, Japan.
  • Tooyama S; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Matsubayashi Y; Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Komatsu T; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Park S; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Okada Y; Schools of Biochemistry and Physiology, Pharmacology & Neuroscience, Faculty of Biomedical Sciences, University of Bristol, Bristol, UK.
  • Takahashi R; Randall Division of Cell and Molecular Biophysics, King's College London, London, UK.
  • Kawano Y; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Hanawa T; Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Iwasaki K; Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
  • Nozaki T; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
  • Torigoe H; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
  • Ikematsu K; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
  • Suzuki Y; Department of Pathology, Sasebo City General Hospital, Sasebo Nagasaki, Japan.
  • Tanaka K; Department of Pharmacology, Faculty of Dentistry, Osaka Dental University, Hirakata Osaka, Japan.
  • Martin P; Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Tokyo, Japan.
  • Shimokawa I; Department of Forensic Pathology and Science, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Mori R; Laboratory of Functional Genomics, Department of Medical Genome Science, Graduate of Frontier Science, The University of Tokyo, Tokyo, Japan.
EMBO Mol Med ; 10(10)2018 10.
Article en En | MEDLINE | ID: mdl-30171089
Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (miR-139-5p, miR-142-3p, miR-142-5p, and miR-223) and show that miR-223 is critical for infection control. miR-223Y/- mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of Staphylococcus aureus-infected wounds. We also showed that the expression of miR-223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/--derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus-infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Infección de Heridas / MicroARNs / Inflamación / Neutrófilos Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Estafilocócicas / Staphylococcus aureus / Infección de Heridas / MicroARNs / Inflamación / Neutrófilos Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido