Volume 31, No 3, Mar 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 3, March 2021: 247-258   |  Open Access

ORIGINAL ARTICLES

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

Qun Chen¹ , Fan Zhang¹ , Lei Dong¹ , Huimin Wu² , Jie Xu¹ , Hanqin Li¹ , Jin Wang¹ , Zhen Zhou¹ , Chunyan Liu¹ , Yanbo Wang¹ , Yuyan Liu¹ , Liangsheng Lu¹ , Chen Wang¹ , Minghui Liu¹ , Xi Chen¹ , Cheng Wang³ , Chunni Zhang³ , Dangsheng Li⁴ , Ke Zen¹ , Fangyu Wang^2,* , Qipeng Zhang^1,* , Chen-Yu Zhang^1,*

¹Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210023, China
²Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
³Department of Clinical Laboratory, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China
⁴Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China
Correspondence: Fangyu Wang(wangf65@nju.edu.cn)Qipeng Zhang(qpzhang@nju.edu.cn)Chen-Yu Zhang(cyzhang@nju.edu.cn)

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.

https://doi.org/10.1038/s41422-020-0389-3

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