α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
- University of California, San Francisco, United States
- University of California, Berkeley, United States
- University Of California, San Francisco, United States
- Hiroshima University, Japan
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.
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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)
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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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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