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Autocrine TGF-ß-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis.
Enomoto, Yasunori; Katsura, Hiroaki; Fujimura, Takashi; Ogata, Akira; Baba, Saori; Yamaoka, Akira; Kihara, Miho; Abe, Takaya; Nishimura, Osamu; Kadota, Mitsutaka; Hazama, Daisuke; Tanaka, Yugo; Maniwa, Yoshimasa; Nagano, Tatsuya; Morimoto, Mitsuru.
Afiliación
  • Enomoto Y; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Katsura H; Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
  • Fujimura T; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Ogata A; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Baba S; Department of Drug Modality Development, Osaka Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., 5-1-35 Saitoaokita, Minoh, 562-0029, Japan.
  • Yamaoka A; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Kihara M; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Abe T; Laboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Nishimura O; Laboratory for Animal Resources and Genetic Engineering (LARGE), RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Kadota M; Laboratory for Animal Resources and Genetic Engineering (LARGE), RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Hazama D; Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Tanaka Y; Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
  • Maniwa Y; Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  • Nagano T; Division of Thoracic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
  • Morimoto M; Division of Thoracic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Nat Commun ; 14(1): 4956, 2023 08 31.
Article en En | MEDLINE | ID: mdl-37653024
The molecular etiology of idiopathic pulmonary fibrosis (IPF) has been extensively investigated to identify new therapeutic targets. Although anti-inflammatory treatments are not effective for patients with IPF, damaged alveolar epithelial cells play a critical role in lung fibrogenesis. Here, we establish an organoid-based lung fibrosis model using mouse and human lung tissues to assess the direct communication between damaged alveolar type II (AT2)-lineage cells and lung fibroblasts by excluding immune cells. Using this in vitro model and mouse genetics, we demonstrate that bleomycin causes DNA damage and activates p53 signaling in AT2-lineage cells, leading to AT2-to-AT1 transition-like state with a senescence-associated secretory phenotype (SASP). Among SASP-related factors, TGF-ß plays an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-ß-positive feedback loop in AT2-lineage cells is a critical cellular system in non-inflammatory lung fibrogenesis. These findings provide insights into the mechanism of IPF and potential therapeutic targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Fibrosis Pulmonar Idiopática Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 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: Factor de Crecimiento Transformador beta / Fibrosis Pulmonar Idiopática Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido