論文 - 詳細
| RRC ID | 76854 |
|---|---|
| 著者 | Enomoto Y, Katsura H, Fujimura T, Ogata A, Baba S, Yamaoka A, Kihara M, Abe T, Nishimura O, Kadota M, Hazama D, Tanaka Y, Maniwa Y, Nagano T, Morimoto M. |
| タイトル | Autocrine TGF-β-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis. |
| ジャーナル | Nat Commun |
| Abstract |
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-β plays an exclusive role in promoting lung fibroblast-to-myofibroblast differentiation. Moreover, the autocrine TGF-β-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. |
| 巻・号 | 14(1) |
| ページ | 4956 |
| 公開日 | 2023-8-31 |
| DOI | 10.1038/s41467-023-40617-y |
| PII | 10.1038/s41467-023-40617-y |
| PMID | 37653024 |
| PMC | PMC10471635 |
| MeSH | Alveolar Epithelial Cells Animals Cell Differentiation Feedback Humans Idiopathic Pulmonary Fibrosis* / genetics Mice Transforming Growth Factor beta* |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 23 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC09921 |