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Elife. 2016 Apr 19;5. pii: e13063. doi: 10.7554/eLife.13063.

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

Author information

1
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
2
Department of Medicine, University of California, San Francisco, San Francisco, United States.
3
Metabolic Biology, University of California, Berkeley, Berkeley, United States.
4
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, United States.
5
Lung Biology Center, University of California, San Francisco, San Francisco, United States.
6
Cell-Matrix Frontier Laboratory, Biomedical Research Unit, Health Administration Center, Hiroshima University, Hiroshima, 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.

KEYWORDS:

Mfge8; PTEN; cell biology; gastrointestinal motility; human; integrin; mouse; nutrient absorption; smooth muscle

PMID:
27092791
PMCID:
PMC4868538
DOI:
10.7554/eLife.13063
[Indexed for MEDLINE]
Free PMC Article

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