Coordinated gastric smooth muscle contraction is critical for proper digestion and is adversely affected by a number of gastric motility disorders. In this study we report that the secreted protein Mfge8 (milk fat globule-EGF factor 8) inhibits the contractile responses of human gastric antrum muscles to cholinergic stimuli by reducing the inhibitory phosphorylation of the MYPT1 (myosin phosphatase-targeting subunit (1) subunit of MLCP (myosin light chain phosphatase), resulting in reduced LC20 (smooth muscle myosin regulatory light chain (2) phosphorylation. Mfge8 reduced the agonist-induced increase in the F-actin/G-actin ratios of β-actin and γ-actin1. We show that endogenous Mfge8 is bound to its receptor, α8β1 integrin, in human gastric antrum muscles, suggesting that human gastric antrum muscle mechanical responses are regulated by Mfge8. The regulation of gastric antrum smooth muscles by Mfge8 and α8 integrin functions as a brake on gastric antrum mechanical activities. Further studies of the role of Mfge8 and α8 integrin in regulating gastric antrum function will likely reveal additional novel aspects of gastric smooth muscle motility mechanisms.

协调的胃平滑肌收缩对于适当的消化至关重要，并且受到许多胃动力障碍的不利影响。在这项研究中，我们报告了分泌蛋白 Mfge8（乳脂肪球-EGF 因子 8）通过降低 MYPT1（肌球蛋白磷酸酶靶向亚基 (1) MLCP（肌球蛋白轻链磷酸酶），导致 LC20（平滑肌肌球蛋白调节轻链 (2) 磷酸化）降低。Mfge8 降低了激动剂诱导的 β-肌动蛋白和 γ-肌动蛋白 1 的 F-肌动蛋白/G-肌动蛋白比率的增加。我们表明，内源性 Mfge8 与其受体 α8β1 整合素在人胃窦肌中结合，表明人胃窦肌机械反应受 Mfge8 调节。Mfge8 和 α8 整合素对胃窦平滑肌的调节起到了抑制胃窦机械活动的作用。进一步研究 Mfge8 和 α8 整合素在调节胃窦功能中的作用可能会揭示胃平滑肌运动机制的其他新方面。