Cellular signals associated with integrin activation in afferent arteriole

Abstract

By pulling fibronectin‐coated magnetic beads to activate integrins in renal vascular smooth muscle cells (VSMCs) grown on flexible substratum, it was found that the traction force exerted on the substratum by VSMC remained elevated after the termination of pulling force. These observations showed that activation of α5β1 integrins (receptors for fibronectin in VSMCs) with mechanical force triggered myogenic‐like behavior in VSMCs. We sought to determine whether antibodies known to activate α5β1 integrins can elicit cellular signals related to myogenic response in VSMCs of perfused afferent arterioles. We monitored VSMC [Ca2+]i with fluo‐4 and ROS (reactive oxygen species) production with CM‐H2DCFD using confocal microscopy. ROS has been implicated in signaling events of myogenic response in other vascular beds. α5‐integrin antibody ( HMα5‐1, 10 μg/ml) induced an initial increase of [Ca2+]i ( 124 ± 8 % of baseline, 35 cells/5 vessels), which was followed by multiple Ca2+ spikes. The increase of [Ca2+]i was associated with reduction of luminal diameter. α5‐integrin antibody also increased ROS production, which reached the peak ( 110 ± 3% of baseline, 7 vessels) at about 30 s after the application. Control antibodies did not trigger Ca2+ mobilization and ROS production. Our observations suggested Ca2+ mobilization is the major response when α5β1 integrins were activated in renal VSMCs. Supported by AHA.