2-APB在防止与逆转血管平滑肌表型转换与增殖中的作用
ttenuation and reversal of vascular smooth muscle phenotypic modulation and proliferation by a CRAC channel inhibitor 2-APB
目的：探索钙释放激活钙（CRAC）通道拮抗剂2-APB在血管平滑肌细胞（vascular smooth muscle cell, VSMC）的表型转换与增殖中的作用。方法：Wistar大鼠胸主动脉VSMC用组织贴块法获得。用10%血清诱导表型转换与增殖。免疫印迹检测CRAC通道两大组分STIM1与Orai1在表型转换过程中的变化。细胞增殖用PI/BrdU双标法检测。结果：增殖期VSMC存在着STIM1与Orai1，是介导钙池操控钙内流（store-operated calcium entry, SOCE）的分子基础。10%血清诱导VSMC表型转换与增殖，后者需要STIM1与Orai1的表达上调。2-APB能够有效抑制并逆转VSMC表型转换与增殖。结论：CRAC通道小分子抑制剂能够有效抑制并逆转VSMC表型转换与增殖，是潜在的抗血管增生性疾病药物。
Objective: To probe the role of 2-aminoethyl diphenylborinate (2-APB), an inhibitor of calcium release-activated calcium (CRAC) channel in phenotypic modulation and proliferation of vascular smooth muscle cell (VSMC). Methods: VSMC was obtained from thoracic aorta of Wistar rat, and phenotypic switching and proliferation was induced by 10% fetal bovine serum (FBS). Dynamics of STIM1 and Orai1 expression was monitored by Western blot during phenotypic modulation. Cell proliferation was measured using the propidium iodine/BrdU double-labeling method. Results: Both STIM1 and Orai1 were expressed in proliferative VSMCs, which mediated store-operated calcium entry (SOCE). FBS-induced phenotypic change and proliferation required expression upregulation of Orai1 and STIM1, and were effectively attenuated or reversed by 2-APB. Conclusion: Small molecule inhibitors of CRAC channel may be promising therapeutic agents for vascular perliferative diseases by preventing and reversing VSMC phenotypic switching and proliferation. (Corresponding authors: stang@nankai.edu.cn or stellarli@nankai.edu.cn)
王腾飞、蔡翔宇、杨亮、Donald L. GILL、李静、王友军、唐向东、于岩
基础医学生理学生物化学
分子药理学血管平滑肌细胞表型转换钙释放激活钙通道2-APB
Molecular pharmacology vascular smooth muscle cell phenotypic switching calcium release-activated calcium channel 2-aminoethyl diphenylborinate (2-APB)
王腾飞,蔡翔宇,杨亮,Donald L. GILL,李静,王友军,唐向东,于岩.2-APB在防止与逆转血管平滑肌表型转换与增殖中的作用[EB/OL].(2012-01-19)[2025-05-26].http://www.paper.edu.cn/releasepaper/content/201201-766.点此复制
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