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

by Chen, Qun , Chen, Xi , Zhou, Zhen , Zhang, Chunni , Zhang, Chen-Yu , Dong, Lei , Zhang, Qipeng , Liu, Yuyan , Zhang, Fan , Wang, Fangyu , Xu, Jie , Wang, Yanbo , Li, Hanqin , Liu, Minghui , Lu, Liangsheng , Li, Dangsheng , Wang, Jin , Wang, Cheng , Wang, Chen , Liu, Chunyan , Zen, Ke , Wu, Huimin

in 13/1 / 13/2 / 13/31 / 14/19 / 14/32 / 14/34 / 38/90 / 38/91 / 45/22 / 45/77 / 631/337/1645/2052 / 631/337/384/331 / 64/60 / Absorption / Administration, Oral / Animals / Biomedical and Life Sciences / Cell Biology / Diet - methods / Female / Fibrosis / Flowers & plants / Gastric Absorption - genetics / Gene expression / HEK293 Cells / Hep G2 Cells / Humans / Life Sciences / Male / Membrane Transport Proteins - genetics / Membrane Transport Proteins - metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / MicroRNAs / MicroRNAs - administration & dosage / MicroRNAs - metabolism / miRNA / Oral administration / Ribonucleic acid / RNA / RNA Transport - genetics / RNA, Plant - administration & dosage / RNA, Plant - metabolism / Stomach / Stomach - metabolism

2021

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2021

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2021

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Journal Article

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

Chen, Qun,

Chen, Xi,

Zhou, Zhen,

Zhang, Chunni,

Zhang, Chen-Yu,

Dong, Lei,

Zhang, Qipeng,

Liu, Yuyan,

Zhang, Fan,

Wang, Fangyu,

Xu, Jie,

Wang, Yanbo,

Li, Hanqin,

Liu, Minghui,

Lu, Liangsheng,

Li, Dangsheng,

Wang, Jin,

Wang, Cheng,

Wang, Chen,

Liu, Chunyan,

Zen, Ke,

Wu, Huimin

2021

Overview

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.

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Publisher

Springer Nature Singapore,Nature Publishing Group

Subject

13/1

/ 13/2

/ 13/31

/ 14/19

/ 14/32

/ 14/34

/ 38/90