Involvement of BK channel in differentiation of vascular smooth muscle cells induced by mechanical stretch |
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| Institution: | 1. Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China;2. Lab of Biomechanics, Department of Engineering Mechanics, Tsinghua University, Beijing, China;3. School of Aerospace Engineering, Beijing Institute of Technology, Beijing, China;1. Department of Physiology & Biophysics, Virginia Commonwealth University, Richmond, Virginia;2. Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia;1. Warwickshire Vascular and Endovascular Unit, University Hospital Coventry and Warwickshire, Coventry, UK;2. Division of Metabolic and Vascular Health, University of Warwick, Coventry, UK;3. Department of Vascular Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece;4. Department of Research and Development, Dudley Group National Health Service Foundation Trust, Russells Hall Hospital, Dudley, UK;1. Eindhoven University of Technology, Polymer Technology, Department of Mechanical Engineering, PO Box 513, 5600 MB Eindhoven, The Netherlands;2. Dutch Polymer Institute (DPI), P.O. Box 902, 5600 AX Eindhoven, The Netherlands |
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| Abstract: | The differentiation of vascular smooth muscle cells (VSMCs), which are exposed to mechanical stretch in vivo, plays an important role in vascular remodeling during hypertension. Here, we demonstrated the mechanobiological roles of large conductance calcium and voltage-activated potassium (BK) channels in this process. In comparison with 5% stretch (physiological), 15% stretch (pathological) induced the de-differentiation of VSMCs, resulting in significantly decreased expressions of VSMC markers, i.e., α-actin, calponin and SM22. The activity of BK channels, assessed by patch clamp recording, was significantly increased by 15% stretch and was accompanied by an increased alternative splicing of BK channel α-subunit at the stress axis-regulated exons (STREX). Furthermore, transfection of whole BK or STREX-deleted BK plasmids revealed that STREX was important for BK channels to sense mechanical stretch. Using thapsigargin (TG) which induces endoplasmic reticulum (ER) stress, and xbp1-targeted siRNA transfection which blocks ER stress, the results revealed that ER stress was contribute to stretch-induced alternative splicing of STREX. Our results suggested that during hypertension, pathological stretch may induce the ER stress in VSMCs, which affects the alternative splicing and activity of BK channels, and subsequently modulates VSMC differentiation. |
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| Keywords: | Vascular smooth muscle cells Differentiation Mechanical stretch BK channel Endoplasmic reticulum stress |
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