Dietary Depletion of Milk Exosomes and Their MicroRNA Cargos Elicits a Depletion of miR-200a-3p and Elevated Intestinal Inflammation and Chemokine (C-X-C Motif) Ligand 9 Expression in Mdr1a-/- Mice

Current Developments in Nutrition
Di WuJanos Zempleni

Abstract

Exosomes transfer regulatory microRNAs (miRs) from donor cells to recipient cells. Exosomes and miRs originate from both endogenous synthesis and dietary sources such as milk. miR-200a-3p is a negative regulator of the proinflammatory chemokine (C-X-C motif) ligand 9 (CXCL9). Male Mdr1a-/- mice spontaneously develop clinical signs of inflammatory bowel disease (IBD). We assessed whether dietary depletion of exosomes and miRs alters the severity of IBD in Mdr1a-/- mice owing to aberrant regulation of proinflammatory cytokines. Starting at 5 wk of age, 16 male Mdr1a-/- mice were fed either milk exosome- and RNA-sufficient (ERS) or milk exosome- and RNA-depleted (ERD) diets. The ERD diet is characterized by a near-complete depletion of miRs and a 60% loss of exosome bioavailability compared with ERS. Mice were killed when their weight loss exceeded 15% of peak body weight. Severity of IBD was assessed by histopathological evaluation of cecum. Serum cytokine and chemokine concentrations and mRNA and miR tissue expression were analyzed by multiplex ELISAs, RNA-sequencing analysis, and qRT-PCR, respectively. Stromal collapse, gland hyperplasia, and additive microscopic disease scores were (mean ± SD) 56.7% ± 23.3%, 23.5% ± 11.8%, and...Continue Reading

Citations

Oct 8, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Sameena WaniCharalabos Pothoulakis
Jun 3, 2021·Animals : an Open Access Journal From MDPI·Bin ZengYongliang Zhang
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Xue JiangXia Chi

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Datasets Mentioned

BETA
PRJNA516639

Methods Mentioned

BETA
light microscopy
Assay
PCR

Software Mentioned

EBseq
Prism
Target Scan Mouse
R
GraphPad

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