Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila.
Musashi expression in intestinal stem cells attenuates radiation-induced decline in intestinal permeability and survival in Drosophila.
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DOI：
10.1038/s41598-020-75867-z
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发表时间：
2020-11-05
影响因子：
4.6
通讯作者：
Kapahi P
中科院分区：
文献类型：
--
作者：
Sharma A;Akagi K;Pattavina B;Wilson KA;Nelson C;Watson M;Maksoud E;Harata A;Ortega M;Brem RB;Kapahi P
暴露于环境因素或治疗（如放射治疗）的遗传毒性应激会减少健康寿命并加速衰老。我们已经建立了一个果蝇模型来研究辐射诱导的损伤和修复的分子效应。利用定量肠道渗透性测定，我们进行了无偏差的GWAS筛选（使用来自果蝇遗传参考小组的156个菌株），以寻找调节果蝇成虫辐射诱导的肠道渗透性的天然遗传变体。黑腹果蝇从这个屏幕上，我们确定了一个RNA结合蛋白，武藏（msi），作为一个可能的基因与辐射后肠道通透性的变化。msi的过度表达促进了肠干细胞的增殖，从而增加了辐射后的存活率，并挽救了辐射诱导的肠通透性。综上所述，我们建立了D。melanogaster作为一种适宜的模型系统来研究辐射诱导的肠损伤对成人的影响，并已将MSI确定为潜在的治疗靶点。
Exposure to genotoxic stress by environmental agents or treatments, such as radiation therapy, can diminish healthspan and accelerate aging. We have developed a Drosophila melanogaster model to study the molecular effects of radiation-induced damage and repair. Utilizing a quantitative intestinal permeability assay, we performed an unbiased GWAS screen (using 156 strains from the Drosophila Genetic Reference Panel) to search for natural genetic variants that regulate radiation-induced gut permeability in adult D. melanogaster. From this screen, we identified an RNA binding protein, Musashi (msi), as one of the possible genes associated with changes in intestinal permeability upon radiation. The overexpression of msi promoted intestinal stem cell proliferation, which increased survival after irradiation and rescued radiation-induced intestinal permeability. In summary, we have established D. melanogaster as an expedient model system to study the effects of radiation-induced damage to the intestine in adults and have identified msi as a potential therapeutic target.
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