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Single-cell RNA sequencing analysis reveals alginate oligosaccharides preventing chemotherapy-induced mucositis.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2020-01-03 , DOI: 10.1038/s41385-019-0248-z
Yong Zhao 1, 2 , Yanni Feng 3 , Ming Liu 1 , Liang Chen 1 , Qingshi Meng 1 , Xiangfang Tang 1 , Shukun Wang 1 , Lei Liu 1 , Lan Li 2 , Wei Shen 2 , Hongfu Zhang 1
Affiliation  

Worldwide the incidence of cancer has been continuing increasing. Mucositis of the gastrointestinal tract is a common side effect in patients under chemotherapy. Anticancer drug busulfan, used for treating chronic myeloid leukemia especially in pediatric patients, causes mucositis of the gastrointestinal tract. Alginate oligosaccharides (AOS) are natural products with attractive pharmaceutical potentials. We aimed to investigate, at the single-cell level, AOS preventing small intestine mucositis induced by busulfan. We found that busulfan disturbed the endoplasmic reticulum and mitochondria of cells in the small intestine, damaged cell membranes especially cell junctions, and disrupted microvilli; all of which were rescued by AOS. Single-cell RNA sequencing analysis and functional enrichment analysis showed that AOS could recover small intestinal function. Deep analysis found that AOS improved the expression of transcriptional factors which explained AOS regulating gene expression to improve small intestine function. Further investigation in IPEC-J2 cells found that AOS acts its function through mannose receptor signaling pathway. Moreover, the improved blood metabolome confirmed small intestinal function was recovered by AOS. As a natural product with many advantages, AOS could be developed to assist in the recovery of intestinal functions in patients undergoing anticancer chemotherapy or other treatments.

中文翻译:

单细胞 RNA 测序分析揭示藻酸盐寡糖可预防化疗引起的粘膜炎。

在世界范围内,癌症的发病率一直在持续上升。胃肠道粘膜炎是化疗患者常见的副作用。用于治疗慢性粒细胞白血病(尤其是儿童患者)的抗癌药白消安会引起胃肠道粘膜炎。藻酸盐低聚糖 (AOS) 是具有诱人药物潜力的天然产物。我们的目的是在单细胞水平上研究 AOS 预防白消安诱导的小肠粘膜炎。我们发现白消安扰乱了小肠细胞的内质网和线粒体,破坏了细胞膜尤其是细胞连接,破坏了微绒毛;都是被AOS救出来的。单细胞RNA测序分析和功能富集分析表明AOS可以恢复小肠功能。深入分析发现 AOS 改善了转录因子的表达,这解释了 AOS 调节基因表达以改善小肠功能。进一步研究IPEC-J2细胞发现AOS通过甘露糖受体信号通路发挥作用。此外,改善的血液代谢组证实小肠功能通过 AOS 恢复。作为一种具有许多优点的天然产物,AOS 可以开发用于帮助接受抗癌化疗或其他治疗的患者恢复肠道功能。深入分析发现 AOS 改善了转录因子的表达,这解释了 AOS 调节基因表达以改善小肠功能。进一步研究IPEC-J2细胞发现AOS通过甘露糖受体信号通路发挥作用。此外,改善的血液代谢组证实小肠功能通过 AOS 恢复。作为一种具有许多优点的天然产物,AOS 可以开发用于帮助接受抗癌化疗或其他治疗的患者恢复肠道功能。深入分析发现 AOS 改善了转录因子的表达,这解释了 AOS 调节基因表达以改善小肠功能。进一步研究IPEC-J2细胞发现AOS通过甘露糖受体信号通路发挥作用。此外,改善的血液代谢组证实小肠功能通过 AOS 恢复。作为一种具有许多优点的天然产物,AOS 可以开发用于帮助接受抗癌化疗或其他治疗的患者恢复肠道功能。
更新日期:2020-01-03
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