Caveolin-1 signaling in lung fibrosis.
Caveolin-1 signaling in lung fibrosis.
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DOI：
10.2174/1874312901206010116
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hoffman S
中科院分区：
文献类型：
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作者：
Tourkina E;Hoffman S
小窝蛋白-1是多种信号级联的主要调节因子，因为它能够结合并抑制多种激酶家族的成员。虽然小窝蛋白-1与小窝相关并参与其形成，但它也存在于其他部位。多项研究表明，小窝蛋白-1可能是肺和其他组织纤维化疾病的一个有用的治疗靶点，因为在这些疾病中，小窝蛋白-1的低水平表达与胶原蛋白的高水平表达和纤维化相关。不仅在分泌胶原蛋白的成纤维细胞中观察到小窝蛋白-1表达降低，在上皮细胞和单核细胞中也是如此。这很有趣，因为上皮细胞和单核细胞都被认为是成纤维细胞的前体。在纤维化中，小窝蛋白-1缺失可能产生的下游效应包括转化生长因子-β信号通路的激活以及单核细胞中CXC趋化因子受体4的上调，导致它们增强向产生其配体CXC趋化因子配体12的受损组织的迁移。最后，在纤维化疾病中，有可能不使用基因疗法来靶向小窝蛋白-1。一种小窝蛋白-1肽（小窝蛋白-1支架结构域）已被确定，它保留了全长分子抑制激酶的功能，并且可以通过添加触角足蛋白内化序列进行修饰，使其能够在体外和体内进入细胞。
Caveolin-1 is a master regulator of several signaling cascades because it is able to bind to and thereby inhibit members of a variety of kinase families. While associated with caveolae and involved in their generation, caveolin-1 is also present at other sites. A variety of studies have suggested that caveolin-1 may be a useful therapeutic target in fibrotic diseases of the lung and other tissues because in these diseases a low level of caveolin-1 expression is associated with a high level of collagen expression and fibrosis. Reduced caveolin-1 expression is observed not only in the fibroblasts that secrete collagen, but also in epithelial cells and monocytes. This is intriguing because both epithelial cells and monocytes have been suggested to be precursors of fibroblasts. Likely downstream effects of loss of caveolin-1 in fibrosis include activation of TGF-β signaling and upregulation of CXCR4 in monocytes resulting in their enhanced migration into damaged tissue where its ligand CXCL12 is produced. Finally, it may be possible to target caveolin-1 in fibrotic diseases without the use of gene therapy. A caveolin-1 peptide (caveolin-1 scaffolding domain) has been identified that retains the function of the full-length molecule to inhibit kinases and that can be modified by addition of the Antennapedia internalization sequence to allow it to enter cells both in vitro and in vivo.