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Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells

European Journal of Nutrition volume 60, pages 317–327 (2021)Cite this article

Abstract

Purpose

Bovine milk exosomes, which are enriched with microRNAs (miRNAs) and proteins, regulate immune response and growth. In the present study, we aimed to assess the protective effects of bovine milk exosomes against oxidative stress of intestinal crypt epithelial cells (IEC-6).

Methods

Bovine milk exosomes were isolated and characterized. To assess the protective effects of exosomes, IEC-6 cells were pretreated with exosomes, followed by H2O2. Cell viability and levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPX), reactive oxidative species (ROS), and lactate dehydrogenase (LDH) were measured. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (Ho1) genes, and miR-146a, miR-155, and the HO-1 protein were also determined.

Results

The isolated bovine milk exosome were positive for CD63 and CD9 expression. The exosomes were approximately circular and had a diameter of about 67.23 nm. Pretreatment of IEC-6 cells with bovine milk exosomes enhanced cell viability; increased SOD and GPX activities; and reduced LDH, ROS, and MDA levels after H2O2 challenge. Further analysis showed that exosome pretreatment increased intracellular miR-146a and miR-155 levels. Exosome pretreatment inhibited the elevation of Nrf2 and Ho1 gene expression induced by H2O2, but promoted HO-1 protein expression.

Conclusion

The results indicated that bovine milk exosomes exerted protective effects against oxidative stress in IEC-6 cells.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China [Grant Number 21476176], the National Key Technology R&D Program of China [Grant Number 2015BAD16B01], the National High Technology Research and Development Program of China [863 Program, Grant Number 2015AA021002], and the International Science and Technology Cooperation Programs of Anhui [Grant Number 1503062006].

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Affiliations

  1. Research Center for Translational Medicine at Shanghai East Hospital, Tongji University School of Medicine, 1239 Siping Road, Shanghai, 200092, People’s Republic of China

    Lanfang Wang, Zhexi Shi, Shu Mu & Xiaoyan Xu

  2. The People’s Hospital of Zhaoyuan City, Zhaoyuan, 265400, Shandong Province, China

    Xinyan Wang

  3. Department of Pathogen Biology, Tongji University School of Medicine, Shanghai, 200092, China

    Li Shen

  4. Research Center for Translational Medicine at Shanghai East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200092, China

    Ping Li

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  1. Lanfang Wang
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  2. Zhexi Shi
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  3. Xinyan Wang
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  4. Shu Mu
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  6. Li Shen
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  7. Ping Li
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Correspondence to Lanfang Wang.

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Wang, L., Shi, Z., Wang, X. et al. Protective effects of bovine milk exosomes against oxidative stress in IEC-6 cells. Eur J Nutr 60, 317–327 (2021). https://doi.org/10.1007/s00394-020-02242-z

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Keywords

  • Exosomes
  • IEC-6 cells
  • Oxidative stress
  • NRF2
  • HO-1
  • microRNA