Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change
Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change
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DOI：
10.1126/science.280.5365.898
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发表时间：
1998-05-08
期刊：
影响因子：
56.9
通讯作者：
Werb, Z
中科院分区：
文献类型：
--
作者：
Kheradmand, F;Werner, E;Werb, Z
整合素介导的细胞形状重组导致细胞表型改变。可溶性抗体与α 5 β 1整联蛋白的结合引发肌动蛋白细胞骨架的破坏，导致兔滑膜成纤维细胞中胶原酶-1基因的表达增加。鸟苷三磷酸结合蛋白Rac 1的激活，这是下游的整合素，是必要的，这一过程中，和激活Rac 1的表达是足以增加胶原酶-1的表达。Rac 1激活产生的活性氧对白细胞介素-1 α的核因子κ B依赖性转录调控至关重要，白细胞介素-1 α以自分泌方式诱导胶原酶-1基因表达。细胞外基质的重塑以及整合素介导的粘附和细胞结构的改变是发育、伤口愈合、炎症和恶性疾病的中心。由此产生的Rac 1的激活可能导致基因调控的改变以及细胞形态发生、迁移和侵袭的改变。
Integrin-mediated reorganization of cell shape leads to an altered cellular phenotype. Disruption of the actin cytoskeleton, initiated by binding of soluble antibody to alpha 5 beta 1 integrin, led to increased expression of the collagenase-1 gene in rabbit synovial fibroblasts. Activation of the guanosine triphosphate-binding protein Rac1, which was downstream of the integrin, was necessary for this process, and expression of activated Rac1 was sufficient to increase expression of collagenase-1. Rac1 activation generated reactive oxygen species that were essential for nuclear factor kappa B-dependent transcriptional regulation of interleukin-1 alpha, which, in an autocrine manner, induced collagenase-1 gene expression. Remodeling of the extracellular matrix and consequent alterations of integrin-mediated adhesion and cytoarchitecture are central to development, wound healing, inflammation, and malignant disease, The resulting activation of Rac1 may lead to altered gene regulation and alterations in cellular morphogenesis, migration, and invasion.