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Has2 Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice.
Sherpa, Mingma Thsering; Kiwamoto, Takumi; Matsuyama, Masashi; Tsunoda, Yoshiya; Yazaki, Kai; Yoshida, Kazufumi; Nakajima, Masayuki; Matsuno, Yosuke; Morishima, Yuko; Ishii, Yukio; Hizawa, Nobuyuki.
Afiliación
  • Sherpa MT; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Kiwamoto T; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Matsuyama M; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Tsunoda Y; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Yazaki K; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Yoshida K; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Nakajima M; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Matsuno Y; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Morishima Y; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Ishii Y; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
  • Hizawa N; Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Front Immunol ; 12: 770305, 2021.
Article en En | MEDLINE | ID: mdl-35069543
HAS2 is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified HAS2 as a candidate gene for increased susceptibility to adult asthma. However, whether HAS2 dysfunction affects airway remodeling and steroid insensitivity is still limited. Therefore, this study aimed to clarify the Has2 dysfunction, triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. Has2 heterozygous-deficient (Has2+/-) mice and their wild-type littermates have been evaluated in a model of chronic ovalbumin (OVA) sensitization and challenge. Mice present a higher sensitivity to OVA and higher IL-17 release as well as eosinophilic infiltration. RNA sequencing demonstrated the downregulation of EIF2 signaling pathways, TGF-ß signaling pathways, and heat shock proteins with Th17 bias in Has2+/--OVA mice. The combined treatment with anti-IL-17A antibody and dexamethasone reduces steroid insensitivity in Has2+/--OVA mice. Has2 attenuation worsens eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling and could potentially be exploited for their therapeutic benefits in patients with asthma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Resistencia a Medicamentos / Remodelación de las Vías Aéreas (Respiratorias) / Hialuronano Sintasas Límite: Animals Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Resistencia a Medicamentos / Remodelación de las Vías Aéreas (Respiratorias) / Hialuronano Sintasas Límite: Animals Idioma: En Revista: Front Immunol Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza