SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs

• 作者: Qun Chen Fan Zhang Lei Dong Huimin Wu Jie Xu Hanqin Li Jin Wang Zhen Zhou Chunyan Liu Yanbo Wang Yuyan Liu Liangsheng Lu Chen Wang Minghui Liu Xi Chen Cheng Wang Chunni Zhang Dangsheng Li Ke Zen Fangyu Wang Qipeng Zhang Chen-Yu Zhang
• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ARTICLES
• 页码范围: 247-258
• 页数: 12页
• 语种: 英文

摘要

Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression,but the absorption mechanism remains unknown.Here,we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs.SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs.Notably,we identified the stomach as the primary site for dietary microRNA absorption,which is dramatically attenuated in the stomachs of SIDT1-deficient mice.Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent.Furthermore,oral administration of plant-derived miR2911 retards liver fibrosis,and this protective effect was abolished in SIDT1-deficient mice.Our findings reveal a major mechanism underlying the absorption of dietary microRNAs,uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.