Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis
PLoS ONE 13 巻 5 号
e0196844- 頁
2018-05-03 発行
アクセス数 : 664 件
ダウンロード数 : 135 件
今月のアクセス数 : 7 件
今月のダウンロード数 : 3 件
この文献の参照には次のURLをご利用ください : https://ir.lib.hiroshima-u.ac.jp/00047661
| ファイル情報(添付) | |
| タイトル ( eng ) |
Inhibition of the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis
|
| 作成者 |
Tamura Ryo
|
| 収録物名 |
PLoS ONE
|
| 巻 | 13 |
| 号 | 5 |
| 開始ページ | e0196844 |
| 抄録 |
Transforming growth factor-β1 (TGF-β1) is a major mediator of peritoneal fibrosis and reportedly affects expression of the H3K4 methyltransferase, SET7/9. SET7/9-induced H3K4 mono-methylation (H3K4me1) critically activates transcription of fibrosis-related genes. In this study, we examined the effect of SET7/9 inhibition on peritoneal fibrosis in mice and in human peritoneal mesothelial cells (HPMCs). We also examined SET7/9 expression in nonadherent cells isolated from the effluent of peritoneal dialysis (PD) patients. Murine peritoneal fibrosis was induced by intraperitoneal injection of methylglyoxal (MGO) into male C57/BL6 mice over 21 days. Sinefungin, a SET7/9 inhibitor, was administered subcutaneously just before MGO injection (10 mg/kg). SET7/9 expression was elevated in both MGO-injected mice and nonadherent cells isolated from the effluent of PD patients. SET7/9 expression was positively correlated with dialysate/plasma ratio of creatinine in PD patients. Sinefungin was shown immunohistochemically to suppress expression of mesenchymal cells and collagen deposition, accompanied by decreased H3K4me1 levels. Peritoneal equilibration tests showed that sinefungin attenuated the urea nitrogen transport rate from plasma and the glucose absorption rate from the dialysate. In vitro, sinefungin suppressed TGF-β1-induced expression of fibrotic markers and inhibited H3K4me1. These findings suggest that inhibiting the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis.
|
| 内容記述 |
This work was supported by the Hiroshima University Grant-in-Aid for Exploratory Research and the grant from Ryokufukai.
|
| 言語 |
英語
|
| 資源タイプ | 学術雑誌論文 |
| 出版者 |
Public Library of Science
|
| 発行日 | 2018-05-03 |
| 権利情報 |
© 2018 Tamura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|
| 出版タイプ | Version of Record（出版社版。早期公開を含む） |
| アクセス権 | オープンアクセス |
| 収録物識別子 |
[ISSN] 1932-6203
[DOI] 10.1371/journal.pone.0196844
[DOI] https://doi.org/10.1371/journal.pone.0196844
|
