Localization of cysteine protease, cathepsin S, to the surface of vascular smooth muscle cells by association with integrin alphanubeta3.
Localization of cysteine protease, cathepsin S, to the surface of vascular smooth muscle cells by association with integrin alphanubeta3.
复制标题
DOI：
--
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
X. Cheng;M. Kuzuya;Kae Nakamura;Qun Di;Zexuan Liu;Takeshi Sasaki;S. Kanda;Hai Jin;G. Shi;T. Murohara;M. Yokota;A. Iguchi
中科院分区：
文献类型：
--
作者：
X. Cheng;M. Kuzuya;Kae Nakamura;Qun Di;Zexuan Liu;Takeshi Sasaki;S. Kanda;Hai Jin;G. Shi;T. Murohara;M. Yokota;A. Iguchi
平滑肌细胞（SMC）从图尼卡中膜迁移到内膜，是新生内膜形成的关键事件，需要富含弹性蛋白的细胞外基质屏障的蛋白水解降解。虽然组织蛋白酶S（Cat S）在动脉粥样硬化和新生内膜病变中过表达，但其在SMC行为中的确切作用主要尚未解决。我们研究了Cat S对SMC通过细胞外基质屏障迁移的影响及其在SMC中的定位。选择性Cat S抑制剂和内源性抑制剂半胱氨酸蛋白酶抑制剂C显著减弱SMC穿过弹性蛋白凝胶的侵袭。蛋白质印迹和细胞表面生物素化分析表明，本地化的28 kd的活性形式的猫S的SMC表面上，与其在亚细胞基质的蛋白水解的作用一致。与对照组相比，干扰素-γ或白细胞介素-β 1治疗显著增强了SMC膜降解弹性蛋白的能力，沿着活性Cat S水平的显著增加。免疫荧光和共聚焦显微镜显示，在SMCs的外周的猫S簇的间断模式，进一步的研究表明，部分共定位的猫S和整合素β 3在细胞表面。这些发现表明，活性Cat S与整合素β 3作为SMC表面的受体共定位，在SMC的侵袭行为中起重要作用。
Smooth muscle cell (SMC) migration from the tunica media to the intima, a key event in neointimal formation, requires proteolytic degradation of elastin-rich extracellular matrix barriers. Although cathepsin S (Cat S) is overexpressed in atherosclerotic and neointimal lesions, its exact role in SMC behavior remains primarily unresolved. We examined the involvement of Cat S on SMC migration through an extracellular matrix barrier and its localization in SMCs. A selective Cat S inhibitor and the endogenous inhibitor cystatin C significantly attenuated SMC invasion across elastin gel. Western blotting and cell surface biotinylation analysis demonstrated localization of the 28-kd active form of Cat S on the SMC surface, consistent with its role in the proteolysis of subcellular matrices. Treatment with interferon-gamma or interleukin-beta1 significantly augmented the ability of SMC membranes to degrade elastin along with a significant increase in the level of active Cat S compared with controls. Immunofluorescence and confocal microscopy showed a punctuated pattern of Cat S clusters at the periphery of SMCs; further studies demonstrated partial co-localization of Cat S and integrin alphanubeta3 at the cell surfaces. These findings demonstrate that active Cat S co-localizes with integrin alphanubeta3 as a receptor on the SMC surface, playing an important role in the invasive behavior of SMCs.