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

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.

• Authors: Amin Khalifeh-Soltani, Arnold Ha, Michael J Podolsky, Donald A McCarthy, William McKleroy, Saeedeh Azary, Stephen Sakuma, Kevin M Tharp, Nanyan Wu, Yasuyuki Yokosaki, Daniel Hart, Andreas Stahl, Kamran Atabai
• Journal: eLife (Elife) Vol. 5 (04 19 2016) ISSN: 2050-084X [Electronic] England
• PMID: 27092791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Surface
• Integrins
• Mfge8 protein, mouse
• Milk Proteins
• integrin alpha8beta1
• PTEN Phosphohydrolase
• Pten protein, mouse

Topics

• Adsorption
• Animals
• Antigens, Surface (metabolism)
• Food
• Gastrointestinal Motility
• Gastrointestinal Tract (physiology)
• Integrins (metabolism)
• Mice
• Milk Proteins (metabolism)
• PTEN Phosphohydrolase (metabolism)