論文 - 詳細
| RRC ID | 79152 |
|---|---|
| 著者 | Katanasaka Y, Yabe H, Murata N, Sobukawa M, Sugiyama Y, Sato H, Honda H, Sunagawa Y, Funamoto M, Shimizu S, Shimizu K, Hamabe-Horiike T, Hawke P, Komiyama M, Mori K, Hasegawa K, Morimoto T. |
| タイトル | Fibroblast-specific PRMT5 deficiency suppresses cardiac fibrosis and left ventricular dysfunction in male mice. |
| ジャーナル | Nat Commun |
| Abstract |
Protein arginine methyltransferase 5 (PRMT5) is a well-known epigenetic regulatory enzyme. However, the role of PRMT5-mediated arginine methylation in gene transcription related to cardiac fibrosis is unknown. Here we show that fibroblast-specific deletion of PRMT5 significantly reduces pressure overload-induced cardiac fibrosis and improves cardiac dysfunction in male mice. Both the PRMT5-selective inhibitor EPZ015666 and knockdown of PRMT5 suppress α-smooth muscle actin (α-SMA) expression induced by transforming growth factor-β (TGF-β) in cultured cardiac fibroblasts. TGF-β stimulation promotes the recruitment of the PRMT5/Smad3 complex to the promoter site of α-SMA. It also increases PRMT5-mediated H3R2 symmetric dimethylation, and this increase is inhibited by Smad3 knockdown. TGF-β stimulation increases H3K4 tri-methylation mediated by the WDR5/MLL1 methyltransferase complex, which recognizes H3R2 dimethylation. Finally, treatment with EPZ015666 significantly improves pressure overload-induced cardiac fibrosis and dysfunction. These findings suggest that PRMT5 regulates TGF-β/Smad3-dependent fibrotic gene transcription, possibly through histone methylation crosstalk, and plays a critical role in cardiac fibrosis and dysfunction. |
| 巻・号 | 15(1) |
| ページ | 2472 |
| 公開日 | 2024-3-19 |
| DOI | 10.1038/s41467-024-46711-z |
| PII | 10.1038/s41467-024-46711-z |
| PMID | 38503742 |
| PMC | PMC10951424 |
| MeSH | Animals Fibroblasts* / metabolism Fibrosis Heart Male Mice Protein-Arginine N-Methyltransferases / genetics Protein-Arginine N-Methyltransferases / metabolism Transforming Growth Factor beta / metabolism Ventricular Dysfunction, Left* / genetics |
| 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 | 4 |
| 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 | |
| 遺伝子材料 | pCMFlag_hsSMAD3 (RDB07019) |