All-trans-retinoic acid attenuates radiation-induced intestinal fibrosis in mice.
All-trans-retinoic acid attenuates radiation-induced intestinal fibrosis in mice.
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DOI：
10.1016/j.jss.2007.12.762
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发表时间：
2008-11
期刊：
影响因子：
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通讯作者：
Kae Okoshi;H. Kubo;S. Nagayama;C. Tabata;Y. Kadokawa;S. Hisamori;Y. Yonenaga;A. Fujimoto;A. Mori;H. Onodera;G. Watanabe;Y. Sakai
中科院分区：
文献类型：
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作者：
Kae Okoshi;H. Kubo;S. Nagayama;C. Tabata;Y. Kadokawa;S. Hisamori;Y. Yonenaga;A. Fujimoto;A. Mori;H. Onodera;G. Watanabe;Y. Sakai
背景：肠道纤维化导致严重的肠蠕动障碍或梗阻是腹部或盆腔放射治疗的一个棘手的不良反应。我们最近报道了全反式维甲酸（ATRA）可以预防辐射或博莱霉素引起的肺纤维化。在这里，我们研究了ATRA对小鼠辐射诱导的肠道纤维化模型的影响。材料与方法我们评估手术标本晚期放射纤维化的组织学。然后，我们通过组织学检查和定量测量辐照小鼠肠组织中白细胞介素-6和转化生长因子-β1 mRNA的含量，并研究ATRA对辐照人肠成纤维细胞转分化和胶原生成的影响。结果人类晚期放射性肠炎标本粘膜下层和浆膜增厚，与小鼠模型一致。ATRA可减轻辐照诱导的肠纤维化，降低白细胞介素-6和转化生长因子-β1的mRNA表达。体外研究表明，ATRA抑制辐照肠成纤维细胞的转分化，并减少细胞中胶原蛋白的产生。结论ATRA可改善辐照诱导的肠纤维化。ATRA可能是治疗慢性放射性肠炎相关纤维化的一种新方法。
BACKGROUNDIntestinal fibrosis leading to severe bowel dysmobility or obstruction is a troublesome adverse effect of abdominal or pelvic radiation therapy. We have recently reported that all-trans-retinoic acid (ATRA) prevents radiation- or bleomycin-induced lung fibrosis. Here, we examined the impact of ATRA on the mouse model of radiation-induced intestinal fibrosis.MATERIALS AND METHODSWe evaluated the histology of late radiation fibrosis in surgical samples. We then performed histological examinations and quantitative measurements of mRNA of interleukin-6 and transforming growth factor-β1in intestinal tissues of irradiated mice with or without intraperitoneal administration of ATRA and investigated the effect of ATRA on the transdifferentiation and the production of collagen of irradiated human intestinal fibroblasts.RESULTSHuman samples of late radiation enteritis showed thickened submucosa and serosa, consistent with mouse model. Administration of ATRA attenuated irradiation-induced intestinal fibrosis and reduced mRNA of interleukin-6 and transforming growth factor-β1. In vitro studies disclosed that ATRA suppressed the transdifferentiation of irradiated intestinal fibroblasts and diminished the production of collagen from the cells.CONCLUSIONSOur findings indicate that ATRA ameliorates irradiation-induced intestinal fibrosis. ATRA could be a novel approach in the treatment of fibrosis associated with chronic radiation enteritis.