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Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

ABSTRACT: Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5? stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5? stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking ?-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5? stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.

SUBMITTER: Ju S

PROVIDER: S-EPMC3702113 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

Ju Songwen S Mu Jingyao J Dokland Terje T Zhuang Xiaoying X Wang Qilong Q Jiang Hong H Xiang Xiaoyu X Deng Zhong-Bin ZB Wang Baomei B Zhang Lifeng L Roth Mary M Welti Ruth R Mobley James J Jun Yan Y Miller Donald D Zhang Huang-Ge HG

Molecular therapy : the journal of the American Society of Gene Therapy 20130611 7

Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorte ...[more]

PMID: 23752315

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Project description:Inflammatory bowel disease is characterized by extensive intestinal inflammation, and therapies against the disease target suppression of the inflammatory cascade. Nutrition has been closely linked to the development and suppression of inflammatory bowel disease, which to a large extent is attributed to the complex immunomodulatory properties of nutrients. Diets containing fish have been suggested to promote health and suppress inflammatory diseases. Even though most of the health-promoting properties of fish-derived nutrients are attributed to fish oil, the potential health-promoting properties of fish protein have not been investigated. Fish sidestreams contain large amounts of proteins, currently unexploited, with potential anti-inflammatory properties, and may possess additional benefits through bioactive peptides and free amino acids. In this project, we utilized fish protein hydrolysates, based on mackerel and salmon heads and backbones, as well as flounder skin collagen. Mice fed with a diet supplemented with different fish sidestream-derived protein hydrolysates (5% w/w) were exposed to the model of DSS-induced colitis. The results show that dietary supplements containing protein hydrolysates from salmon heads suppressed chemically-induced colitis development as determined by colon length and pro-inflammatory cytokine production. To evaluate colitis severity, we measured the expression of different pro-inflammatory cytokines and chemokines and found that the same supplement suppressed the pro-inflammatory cytokines IL-6 and TNFα and the chemokines Cxcl1 and Ccl3. We also assessed the levels of the anti-inflammatory cytokines IL-10 and Tgfb and found that selected protein hydrolysates induced their expression. Our findings demonstrate that protein hydrolysates derived from fish sidestreams possess anti-inflammatory properties in the model of DSS-induced colitis, providing a novel underexplored source of health-promoting dietary supplements.

Dataset Information

Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

Publications

Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis.

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