Non-Random Distribution and Sensory Functions of Primary Cilia in Vascular Smooth Muscle Cells

摘要

Although primary cilia are increasingly recognized to play sensory roles in several cellular systems, their role in vascular smooth muscle cells (VSMCs) has not been defined. We examined in situ position/orientation of primary cilia and ciliary proteins in VSMCs and tested the hypothesis that primary cilia of VSMCs exert sensory functions. By immunofluorescence and electron microscopic imaging, primary cilia of VSMCs were positioned with their long axis aligned at 58.3° angle in relation to the cross-sectional plane of the artery, projecting into the extracellular matrix (ECM). Polycystin-1, polycystin-2 and α3- and β1-integrins are present in cilia. In scratch wound experiments, the majority of cilia were repositioned to the cell-wound interface. Such repositioning was largely abolished by a β1-integrin blocker. Moreover, compared to non-ciliated/deciliated cells, ciliated VSMCs showed more efficient migration in wound repair. Lastly, when directly stimulated with collagen (an ECM component and cognate ligand for α3β1-integrins) or induced ciliary deflection, VSMCs responded with a rise in [Ca²⁺]i that is dependent on the presence of cilia. Taken together, primary cilia of VSMCs are preferentially oriented, possess proteins critical for cell-ECM interaction and mechanosensing and respond to ECM protein and mechanical stimulations. These observations suggest a role for primary cilia in mechanochemical sensing in vasculature.