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miR-802 regulates Paneth cell function and enterocyte differentiation in the mouse small intestine

Author

Listed:
  • Algera Goga

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Büsra Yagabasan

    (Institute of Molecular Health Sciences, ETH Zurich
    Section on Vascular Cell Biology, Joslin Diabetes Center and Department of Medicine, Harvard Medical School)

  • Karolin Herrmanns

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Svenja Godbersen

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Pamuditha N. Silva

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Remy Denzler

    (Institute of Molecular Health Sciences, ETH Zurich
    Astra Zeneka, Section Oncology & Hematology, Baar)

  • Mirjam Zünd

    (Laboratory of Microbiome Research, Institute of Microbiology and Swiss Institute of Bioinformatics, ETH Zürich)

  • Markus Furter

    (Institute of Microbiology, ETH Zurich)

  • Gerald Schwank

    (Universität Zürich)

  • Shinichi Sunagawa

    (Laboratory of Microbiome Research, Institute of Microbiology and Swiss Institute of Bioinformatics, ETH Zürich)

  • Wolf-Dietrich Hardt

    (Institute of Microbiology, ETH Zurich)

  • Markus Stoffel

    (Institute of Molecular Health Sciences, ETH Zurich
    University of Zürich)

Abstract

The intestinal epithelium is a complex structure that integrates digestive, immunological, neuroendocrine, and regenerative functions. Epithelial homeostasis is maintained by a coordinated cross-talk of different epithelial cell types. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here we show that the intestine-enriched miR-802 is a central regulator of intestinal epithelial cell proliferation, Paneth cell function, and enterocyte differentiation. Genetic ablation of mir-802 in the small intestine of mice leads to decreased glucose uptake, impaired enterocyte differentiation, increased Paneth cell function and intestinal epithelial proliferation. These effects are mediated in part through derepression of the miR-802 target Tmed9, a modulator of Wnt and lysozyme/defensin secretion in Paneth cells, and the downstream Wnt signaling components Fzd5 and Tcf4. Mutant Tmed9 mice harboring mutations in miR-802 binding sites partially recapitulate the augmented Paneth cell function of mice lacking miR-802. Our study demonstrates a broad miR-802 network that is important for the integration of signaling pathways of different cell types controlling epithelial homeostasis in the small intestine.

Suggested Citation

  • Algera Goga & Büsra Yagabasan & Karolin Herrmanns & Svenja Godbersen & Pamuditha N. Silva & Remy Denzler & Mirjam Zünd & Markus Furter & Gerald Schwank & Shinichi Sunagawa & Wolf-Dietrich Hardt & Mark, 2021. "miR-802 regulates Paneth cell function and enterocyte differentiation in the mouse small intestine," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23298-3
    DOI: 10.1038/s41467-021-23298-3
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    Cited by:

    1. Mary P. LaPierre & Katherine Lawler & Svenja Godbersen & I. Sadaf Farooqi & Markus Stoffel, 2022. "MicroRNA-7 regulates melanocortin circuits involved in mammalian energy homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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