論文 - 詳細
| RRC ID | 86994 |
|---|---|
| 著者 | Funagura N, Koga T, Etoh K, Hong S, Ichiyasu H, Fujijwara Y, Yasunaga KI, Usuki S, Noda A, Sagara A, Hino S, Komohara Y, Sakagami T, Inoue T, Nakao M. |
| タイトル | Histone demethylase KDM7A negatively regulates fibrotic macrophage polarization and lung fibrosis progression. |
| ジャーナル | Commun Biol |
| Abstract |
Macrophage polarization shapes immune responses in inflammation and fibrosis, yet the epigenetic mechanisms restraining pathogenic states remain unclear. Here, we identify lysine-specific demethylase 7 A (KDM7A) as an epigenetic suppressor of a profibrotic macrophage (Fib-Mac). Using macrophage assays, single-cell RNA sequencing of Kdm7a-knockout mice, and lung tissue from fibrosis patients, we show that Kdm7a loss drives transcriptional and metabolic reprogramming toward Fib-Mac states. Kdm7a-knockout mice exhibit exacerbated bleomycin-induced lung fibrosis with the expansion of Fib-Mac populations. Mechanistically, we identify toll-like receptor 8 (TLR8) as a suppressor of Fib-Mac polarization whose expression is regulated by KDM7A via the repressive mark H3K27me2 at its enhancer. Notably, macrophage Kdm7a and Tlr8 expression declines with age in male mice, consistent with clinical risk patterns. These findings uncover an epigenetic mechanism restraining disease-driving macrophage states and suggest the KDM7A-TLR8 axis as a potential therapeutic target in fibrotic disorders. |
| 巻・号 | 9(1) |
| 公開日 | 2026-1-23 |
| DOI | 10.1038/s42003-026-09610-1 |
| PII | 10.1038/s42003-026-09610-1 |
| PMID | 41578150 |
| PMC | PMC12932667 |
| MeSH | Animals Bleomycin Disease Progression Epigenesis, Genetic Histone Demethylases* / genetics Histone Demethylases* / metabolism Humans Jumonji Domain-Containing Histone Demethylases* / genetics Jumonji Domain-Containing Histone Demethylases* / metabolism Macrophages* / metabolism Macrophages* / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Pulmonary Fibrosis* / chemically induced Pulmonary Fibrosis* / genetics Pulmonary Fibrosis* / metabolism Pulmonary Fibrosis* / pathology |
| IF | 4.165 |
| 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 | 19 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.3 |
| リソース情報 | |
| 遺伝子材料 | pENTR4-H1tetOx1 (RDB07916) CS-RfA-ETBsd (RDB07917) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |