PMID- 25481230 OWN - NLM STAT- MEDLINE DCOM- 20150918 LR - 20151119 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 59 DP - 2015 Feb TI - Involvement of BK channel in differentiation of vascular smooth muscle cells induced by mechanical stretch. PG - 21-9 LID - S1357-2725(14)00376-8 [pii] LID - 10.1016/j.biocel.2014.11.011 [doi] AB - 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., alpha-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 alpha-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. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Wan, Xue-Jiao AU - Wan XJ AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Zhao, Hu-Cheng AU - Zhao HC AD - Lab of Biomechanics, Department of Engineering Mechanics, Tsinghua University, Beijing, China. FAU - Zhang, Ping AU - Zhang P AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Huo, Bo AU - Huo B AD - School of Aerospace Engineering, Beijing Institute of Technology, Beijing, China. FAU - Shen, Bao-Rong AU - Shen BR AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Yan, Zhi-Qiang AU - Yan ZQ AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. FAU - Qi, Ying-Xin AU - Qi YX AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. Electronic address: qiyx@sjtu.edu.cn. FAU - Jiang, Zong-Lai AU - Jiang ZL AD - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141204 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (Biomarkers) RN - 0 (Large-Conductance Calcium-Activated Potassium Channels) RN - 0 (Protein Subunits) RN - 67526-95-8 (Thapsigargin) RN - SY7Q814VUP (Calcium) SB - IM MH - Alternative Splicing/drug effects/genetics MH - Animals MH - Biomarkers/metabolism MH - Calcium/metabolism MH - *Cell Differentiation/drug effects MH - Endoplasmic Reticulum Stress/drug effects MH - Exons/genetics MH - HEK293 Cells MH - Humans MH - Ion Channel Gating/drug effects MH - Large-Conductance Calcium-Activated Potassium Channels/*metabolism MH - Muscle, Smooth, Vascular/*cytology MH - Myocytes, Smooth Muscle/*cytology/drug effects/*metabolism MH - Protein Subunits/metabolism MH - Rats, Sprague-Dawley MH - *Stress, Mechanical MH - Thapsigargin/pharmacology OTO - NOTNLM OT - BK channel OT - Differentiation OT - Endoplasmic reticulum stress OT - Mechanical stretch OT - Vascular smooth muscle cells EDAT- 2014/12/08 06:00 MHDA- 2015/09/19 06:00 CRDT- 2014/12/08 06:00 PHST- 2014/08/07 00:00 [received] PHST- 2014/11/13 00:00 [revised] PHST- 2014/11/25 00:00 [accepted] PHST- 2014/12/08 06:00 [entrez] PHST- 2014/12/08 06:00 [pubmed] PHST- 2015/09/19 06:00 [medline] AID - S1357-2725(14)00376-8 [pii] AID - 10.1016/j.biocel.2014.11.011 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2015 Feb;59:21-9. doi: 10.1016/j.biocel.2014.11.011. Epub 2014 Dec 4.