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

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 mo...

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Main 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
Format:	Article
Language:	English
Published:	eLife Sciences Publications Ltd 2016-04-01
Series:	eLife
Subjects:	integrin Mfge8 PTEN nutrient absorption gastrointestinal motility smooth muscle
Online Access:	https://elifesciences.org/articles/13063

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spelling	doaj-a93fa32e2c4441bca4a189ebfc3b3c4f2021-05-05T00:21:33ZengeLife Sciences Publications LtdeLife2050-084X2016-04-01510.7554/eLife.13063α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanismAmin Khalifeh-Soltani0Arnold Ha1Michael J Podolsky2Donald A McCarthy3William McKleroy4Saeedeh Azary5Stephen Sakuma6Kevin M Tharp7Nanyan Wu8Yasuyuki Yokosaki9Daniel Hart10Andreas Stahl11Kamran Atabai12https://orcid.org/0000-0001-8170-7881Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesMetabolic Biology, University of California, Berkeley, Berkeley, United States; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, United StatesLung Biology Center, University of California, San Francisco, San Francisco, United StatesCell-Matrix Frontier Laboratory, Biomedical Research Unit, Health Administration Center, Hiroshima University, Hiroshima, JapanCardiovascular Research Institute, University of California, San Francisco, San Francisco, United StatesMetabolic Biology, University of California, Berkeley, Berkeley, United States; Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, United StatesCardiovascular Research Institute, University of California, San Francisco, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United States; Lung Biology Center, University of California, San Francisco, San Francisco, United StatesCoordinated 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.https://elifesciences.org/articles/13063integrinMfge8PTENnutrient absorptiongastrointestinal motilitysmooth muscle
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	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
spellingShingle	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 α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism eLife integrin Mfge8 PTEN nutrient absorption gastrointestinal motility smooth muscle
author_facet	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
author_sort	Amin Khalifeh-Soltani
title	α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
title_short	α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
title_full	α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
title_fullStr	α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
title_full_unstemmed	α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism
title_sort	α8β1 integrin regulates nutrient absorption through an mfge8-pten dependent mechanism
publisher	eLife Sciences Publications Ltd
series	eLife
issn	2050-084X
publishDate	2016-04-01
description	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.
topic	integrin Mfge8 PTEN nutrient absorption gastrointestinal motility smooth muscle
url	https://elifesciences.org/articles/13063
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α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism

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