論文 - 詳細
| RRC ID | 72128 |
|---|---|
| 著者 | Ju N, Hayashi H, Shimamura M, Baba S, Yoshida S, Morishita R, Rakugi H, Nakagami H. |
| タイトル | Prevention of bleomycin-induced pulmonary fibrosis by a RANKL peptide in mice. |
| ジャーナル | Sci Rep |
| Abstract |
Despite the recent therapeutic developments for the treatment of pulmonary fibrosis, its prognosis is still not well controlled, and a novel therapeutic agent is needed. Recently, the critical role of Toll-like receptors (TLRs) in the pathophysiology of pulmonary fibrosis has been reported; however, the effects of multiple TLR signaling inhibition are still unknown. Here, we examined how the inhibition of multiple TLRs affects pulmonary fibrosis using a novel synthetic receptor activator of nuclear factor κB ligand (RANKL) partial peptide, MHP1-AcN, which could suppress TLR2, 3, 4, 7, and 9 signaling through CD14 and RANK. When MHP1-AcN was administered in the bleomycin-induced lung fibrosis model, reduced collagen deposition was observed, with suppressed fibrosis-related gene expression including Col1a1, Col1a2, Acta2, Tgfb1 and Tgfbr2. MHP1-AcN also decreased proinflammatory M1 and profibrotic M2 macrophage marker expression. Furthermore, MHP1-AcN treatment inhibited transforming growth factor (TGF-β)-induced Smad2/3 phosphorylation and myofibroblast differentiation in human fetal lung fibroblast (MRC-5) cells. This effect was associated with decreased TGF-β receptor levels and the upregulated Bmp7 and Smad7 expression. These findings suggest that MHP1-AcN protects mice against bleomycin-induced pulmonary fibrosis. MHP1-AcN might provide a novel therapeutic strategy for the pulmonary fibrosis. |
| 巻・号 | 12(1) |
| ページ | 12474 |
| 公開日 | 2022-7-21 |
| DOI | 10.1038/s41598-022-16843-7 |
| PII | 10.1038/s41598-022-16843-7 |
| PMID | 35864207 |
| PMC | PMC9304352 |
| MeSH | Animals Bleomycin / metabolism Bleomycin / toxicity Fibroblasts / metabolism Humans Lung / pathology Mice Mice, Inbred C57BL Peptides / metabolism Pulmonary Fibrosis* / chemically induced Pulmonary Fibrosis* / metabolism Pulmonary Fibrosis* / prevention & control RANK Ligand / metabolism Transforming Growth Factor beta / metabolism |
| IF | 3.998 |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ヒト・動物細胞 | MRC-5(RCB0218) |