論文 - 詳細
| RRC ID | 67517 |
|---|---|
| 著者 | Kaihara K, Nakagawa S, Arai Y, Inoue H, Tsuchida S, Fujii Y, Kamada Y, Kishida T, Mazda O, Takahashi K. |
| タイトル | Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Hypoxia inducible factor (HIF)-1α has been implicated in the pathogenesis of rheumatoid arthritis (RA). HIF-1α, which is expressed in hypoxia, is reversely suppressed in sustained hypoxia. Here, we investigated the inhibitory effect of hypoxia on arthritis by controlling HIF-1α. Rheumatoid fibroblast-like synoviocyte MH7A cells were cultured in a hypoxic incubator for up to 72 h to evaluate the expression of HIF-1. Furthermore, collagen-induced arthritis (CIA) model rats were maintained under 12% hypoxia in a hypoxic chamber for 28 days to evaluate the effect on arthritis. In MH7A cells, HIF-1α protein level increased at 3 h, peaked at 6 h, and subsequently decreased in a time-dependent manner. The transcription of pro-inflammatory cytokines increased at 1 h; however, they decreased after 3 h (p < 0.05). Deferoxamine-mediated activation of HIF-1α abolished the inhibitory effect of sustained hypoxia on pro-inflammatory cytokines. In the rat CIA model, the onset of joint swelling was delayed and arthritis was suppressed in the hypoxia group compared with the normoxia group (p < 0.05). Histologically, joint destruction was suppressed primarily in the cartilage. Thus, sustained hypoxia may represent a new safe, and potent therapeutic approach for high-risk patients with RA by suppressing HIF-1α expression. |
| 巻・号 | 22(8) |
| 公開日 | 2021-4-9 |
| DOI | 10.3390/ijms22083898 |
| PII | ijms22083898 |
| PMID | 33918929 |
| PMC | PMC8068944 |
| MeSH | Animals Arthritis, Rheumatoid / etiology* Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Biomarkers Cell Hypoxia Cells, Cultured Cytokines / genetics Cytokines / metabolism Disease Susceptibility Fibroblasts / metabolism Gene Expression Hypoxia / genetics Hypoxia / metabolism* Hypoxia / pathology Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Inflammation Mediators / metabolism Rats Synoviocytes / metabolism Synoviocytes / pathology |
| IF | 4.556 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |