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
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23298-3. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.