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SCIENCE CHINA Life Sciences, Volume 61, Issue 7: 800-807(2018) https://doi.org/10.1007/s11427-018-9310-7

BMP signaling in homeostasis, transformation and inflammatory response of intestinal epithelium

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  • ReceivedMar 6, 2018
  • AcceptedApr 3, 2018
  • PublishedMay 29, 2018

Abstract

Intestine is the organ for food digestion, nutrient absorption and pathogen defense, in which processes intestinal epithelium plays a central role. Intestinal epithelium undergoes fast turnover, and its homeostasis is regulated by multiple signaling pathways, including Wnt, Notch, Hippo and BMP pathways. BMP signaling has been shown to negatively regulate self-renewal of Lgr5+ intestinal stem cells, constrains the expansion of intestinal epithelium, therefore attenuating colorectal cancer formation. BMPs and their receptors are expressed in both epithelial and mesenchymal cells, suggesting a two-way interaction between the mesenchyme and epithelium. In this review, we summarize the current understanding of the function of BMP signaling in homeostasis, cancerous transformation and inflammatory response of intestinal epithelium.


Funded by

the National Natural Science Foundation of China(31330049)

grants from the National Key Research and Development Program of China(2017YFA0103601)


Acknowledgment

This work was supported by grants from the National Key Research and Development Program of China (2017YFA0103601) and the National Natural Science Foundation of China (31330049) to YGC.


Interest statement

The author(s) declare that they have no conflict of interest.


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  • Figure 1

    The BMP signaling pathway. Upon binding to extracellular BMPs, BMPRII phosphorylates and activates BMPRI, which in turn phosphorylates downstream Smad1/5/8. The R-Smad proteins form a complex with Smad4 and are accumulated in the nucleus to regulate target gene transcription. Noggin and Gremlin 1 associate with BMPs in the extracellular compartment and prevent their binding to the receptors.

  • Figure 2

    The function of BMP signaling in intestine. Left panel: Under the physiological condition, a high level of Noggin in the bottom of crypts shapes a BMP signaling gradient from the crypt to the villus tip. BMP signaling prevents cell proliferation, suppresses intestinal stem cell self-renewal and promotes secretory cell differentiation. Right panel: Disruption of BMP singling in epithelial cells results in epithelial cell proliferation and intestinal stem cell expansion. BMPRIA knockout induces epithelial cell transformation and polyps formation in a long term. Moreover, blockage of BMP signaling in mesenchymal cells leads to hyperproliferation of intestinal stem cells and polyp formation by changing the stem cell niche.

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