研究課題
1.We newly detected “factor A” secreted from mesenchymal stem cells (MSCs), inhibits radiation-induced intestinal epithelial and endothelial cell death. The factor A secretion was enhanced by calcineurin inhibitors which induces intestinal vascular and epithelial cell damage causing gastrointestinal syndrome (GIS). The GIS is critical for some patients to receive total body or abdominal radiation therapy in blood stem cell transplantation or abdominal cancers. Therefore, Factor A or MSC cytotherapy may prevent radiation-induced GIS (paper, in submission).2.We examined a functional analysis of “factor B”, one of inhibitors of apoptotic proteins (IAP), involved in exosomes secreted from MSCs. We found that factor B is acetylated in cells. This finding lead us to examine whether acetylation status of factor B affects its function as an IAP. We focused on radiation effects on a relationship between factor B and its acetylation status. Radiation decreased acetylation levels of factor B in cells through decreasing association with histone acetyltransferase. Low-acetylated levels of factor B could not inhibit caspase-3 activity in vitro. We generated several factor B constructs with substitutions of acetylation sites. Transfection assays using these generated constructs revealed that acetylated factor B (wild type) inhibits radiation-induced cell death, whereas mutant ones lost its inhibitory ability. These findings indicates that acetylation status of factor B is critical for radiation effects on cell viability (paper, under preparation).
2: おおむね順調に進展している
放射線障害組織を軽減・再生する間葉系幹細胞とその放出因子を同定・機能解析している。2種類の因子の同定と機能解析が終了した。現在、幾つかの因子について同定、機能解析を進めており概ね順調に推移していると判断した。
機能分子の同定、機能解析を進めると共に、モデル動物での検証実験を行う予定である。
すべて 2015 2014
すべて 雑誌論文 (3件) (うち査読あり 3件、 謝辞記載あり 1件) 学会発表 (6件)
Eur J Haematol.
巻: 10 ページ: 12536
10.1111/ejh.12536
Biomedical Research (Tokyo)
巻: ３５ ページ: ６１－６８
IJID
巻: ２４ ページ: １１－１３
