TY - JOUR TI - α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism AU - Khalifeh-Soltani, Amin AU - Ha, Arnold AU - Podolsky, Michael J AU - McCarthy, Donald A AU - McKleroy, William AU - Azary, Saeedeh AU - Sakuma, Stephen AU - Tharp, Kevin M AU - Wu, Nanyan AU - Yokosaki, Yasuyuki AU - Hart, Daniel AU - Stahl, Andreas AU - Atabai, Kamran A2 - Ivaska, Johanna VL - 5 PY - 2016 DA - 2016/04/19 SP - e13063 C1 - eLife 2016;5:e13063 DO - 10.7554/eLife.13063 UR - https://doi.org/10.7554/eLife.13063 AB - 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. KW - integrin KW - Mfge8 KW - PTEN KW - nutrient absorption KW - gastrointestinal motility KW - smooth muscle JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -