alpha 8 beta 1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism

作者：Khalifeh Soltani Amin; Ha Arnold; Podolsky Michael J; McCarthy Donald A; McKleroy William; Azary Saeedeh; Sakuma Stephen; Tharp Kevin M; Wu Nanyan; Yokosaki Yasuyuki; Hart Daniel; Stahl Andreas; Atabai Kamran

来源：eLife, 2016, 5: e13063.

DOI：10.7554/eLife.13063

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 alpha 8 beta 1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of alpha 8 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 alpha 8 beta 1 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 alpha 8 beta 1 in regulating gastrointestinal motility and identify alpha 8 as a potential target for disorders characterized by hypo- or hyper-motility.

• 出版日期2016-4-19