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

Qun Chen1, Fan Zhang1, Lei Dong1

  • 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.

Cell Research
|August 18, 2020
PubMed

Insights

Dietary microRNAs are absorbed in the stomach via SIDT1, a protein on gastric pit cells. This discovery explains how microRNAs enter the body and could lead to new oral small RNA therapies.

Area of Science:

  • Molecular Biology
  • Gastroenterology
  • Genetics

Background:

  • Dietary microRNAs can regulate host gene expression in mammals.
  • The mechanism of dietary microRNA absorption remains largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of dietary microRNA absorption.
  • To identify the primary site of dietary microRNA absorption.
  • To investigate the role of SIDT1 in dietary microRNA uptake.

Main Methods:

  • Utilized SIDT1-deficient mice to study microRNA absorption.
  • Performed mechanistic analyses of exogenous microRNA uptake by gastric pit cells.
  • Investigated the effect of plant-derived miR2911 on liver fibrosis in vivo.

Main Results:

  • SIDT1 on gastric pit cells is essential for dietary microRNA absorption.
  • The stomach is the primary site for dietary microRNA absorption.
  • MicroRNA uptake by gastric pit cells is SIDT1 and low-pH dependent.
  • Oral miR2911's protective effect against liver fibrosis is abolished in SIDT1-deficient mice.

Conclusions:

  • SIDT1 mediates dietary microRNA absorption in the stomach.
  • This study reveals a key mechanism for dietary microRNA uptake and identifies the stomach's crucial role.
  • Findings support the development of oral small RNA therapeutics.

Related Concept Videos

Microvilli00:55

Microvilli

Microvilli are tiny finger-like projections found on the surface of certain cells. Their purpose is to increase the surface area of the cell's apical surface, resulting in more effective absorption or secretion of substances.
These microvilli are predominantly present in cells lining the small intestine, kidney tubules, and certain cells in the respiratory and reproductive systems. By significantly expanding the surface area of the cell membrane, microvilli enhance the cell's capacity...
8.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.6K
Drug Absorption: Factors Affecting GI Absorption01:19

Drug Absorption: Factors Affecting GI Absorption

The process of oral drug absorption can be influenced by several factors. Weakly acidic drugs tend to be absorbed more readily from the stomach due to their nonionized state. However, absorption may be less efficient in the upper intestine, where drugs are often ionized. Interestingly, despite the stomach's apparent advantage for drug absorption, its mucous layer can hinder diffusion. Its surface area is also smaller than the intestine's, which can further slow down the absorption rate.
5.6K
Fungal Phylum Microsporidia01:28

Fungal Phylum Microsporidia

Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
306
Factors Influencing Drug Absorption: Anatomical Parameters01:23

Factors Influencing Drug Absorption: Anatomical Parameters

Drug absorption involves the movement of drugs from the point of administration into the systemic circulation. Initially, Gastrointestinal (GI) motility propels the drug through the digestive tract and into the stomach. However, the stomach's high acidity and limited surface area restrict its role in drug absorption for most drugs. The drug then moves from the stomach to the small intestine via gastric emptying, which can be slowed by various factors, including interactions with other...
475