1. Cell Biology

α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism

  1. Amin Khalifeh-Soltani
  2. Arnold Ha
  3. Michael J Podolsky
  4. Donald A McCarthy
  5. William McKleroy
  6. Saeedeh Azary
  7. Stephen Sakuma
  8. Kevin M Tharp
  9. Nanyan Wu
  10. Yasuyuki Yokosaki
  11. Daniel O Hart
  12. Andreas Stahl
  13. Kamran Atabai  Is a corresponding author
  1. University of California, San Francisco, United States
  2. University of California, Berkeley, United States
  3. University Of California, San Francisco, United States
  4. Hiroshima University, Japan
https://doi.org/10.7554/eLife.13063
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Cite this article
  1. Amin Khalifeh-Soltani
  2. Arnold Ha
  3. Michael J Podolsky
  4. Donald A McCarthy
  5. William McKleroy
  6. Saeedeh Azary
  7. Stephen Sakuma
  8. Kevin M Tharp
  9. Nanyan Wu
  10. Yasuyuki Yokosaki
  11. Daniel O Hart
  12. Andreas Stahl
  13. Kamran Atabai
(2016)
α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
eLife 5:e13063.
https://doi.org/10.7554/eLife.13063
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  3. Download .RIS

Abstract

Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8β1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8β1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo- or hyper-motility.

Article and author information

Author details

  1. Amin Khalifeh-Soltani

    Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Arnold Ha

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Michael J Podolsky

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Donald A McCarthy

    Department of Medicine, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. William McKleroy

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Saeedeh Azary

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Stephen Sakuma

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Kevin M Tharp

    Metabolic Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Nanyan Wu

    Lung Biology Center, University Of California, San Francisco, San Fransico, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. Yasuyuki Yokosaki

    Cell-Matrix Frontier Laboratory, Biomedical Research Unit, Health Administration Center, Hiroshima University, Hiroshima, Japan
    Competing interests
    The authors declare that no competing interests exist.

  11. Daniel O Hart

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Andreas Stahl

    Metabolic Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  13. Kamran Atabai

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    For correspondence
    kamran.atabai@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Johanna Ivaska, University of Turku, Finland

Ethics

Animal experimentation: All animal experiments were approved by the UCSF Institutional Animal Care and Use Committee in adherence to NIH guidelines and policies.(#AN109941-01A)

Version history

  1. Received: November 14, 2015
  2. Accepted: April 18, 2016
  3. Accepted Manuscript published: April 19, 2016 (version 1)
  4. Version of Record published: May 16, 2016 (version 2)

Copyright

© 2016, Khalifeh-Soltani et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Amin Khalifeh-Soltani
  2. Arnold Ha
  3. Michael J Podolsky
  4. Donald A McCarthy
  5. William McKleroy
  6. Saeedeh Azary
  7. Stephen Sakuma
  8. Kevin M Tharp
  9. Nanyan Wu
  10. Yasuyuki Yokosaki
  11. Daniel O Hart
  12. Andreas Stahl
  13. Kamran Atabai
(2016)
α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
eLife 5:e13063.
https://doi.org/10.7554/eLife.13063

Share this article

https://doi.org/10.7554/eLife.13063

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