Sánchez-Capelo Amelia
Servicio Neurobiología-Investigación, Hospital Ramón y Cajal, Ctra. Colmenar Viejo Km 9, 28034 Madrid, Spain.
Cytokine Growth Factor Rev. 2005 Feb;16(1):15-34. doi: 10.1016/j.cytogfr.2004.11.002. Epub 2005 Jan 25.
The exposure of cells to TGF-beta1 can trigger a variety of cellular responses including the inhibition of cell growth, migration, differentiation and apoptosis. TGF-beta1-regulated apoptosis is cell type and context-dependent, indeed TGF-beta1 provides signals for both cell survival or apoptosis. The molecular mechanisms underlying the role of TGF-beta1 in apoptosis remains unclear. The proteins that primarily mediate the intracellular signaling of TGF-beta1 are the members of the Smad family. Nevertheless, TGF-beta1 signaling can also cooperate with the death receptor apoptotic pathway (Fas, TNF), with the intracellular modulators of apoptosis JNK and p38 MAP kinases, Akt, NF-kappaB, and with the mitochondrial apoptotic pathway mediated by members of the Bcl-2 family. Moreover, the involvement of TGF-beta1 in the production of oxidative stress and in preventing the inflammatory processes required for the clearance of apoptotic bodies is further evidence of its integration into apoptotic pathways. The interaction and balance between different stimuli provides the basis for the pro- or anti-apoptotic output of TGF-beta1 signaling in a given cell.
细胞暴露于转化生长因子β1（TGF-β1）可引发多种细胞反应，包括抑制细胞生长、迁移、分化和凋亡。TGF-β1调节的凋亡具有细胞类型和环境依赖性，实际上TGF-β1为细胞存活或凋亡都提供信号。TGF-β1在凋亡中作用的分子机制仍不清楚。主要介导TGF-β1细胞内信号传导的蛋白质是Smad家族成员。然而，TGF-β1信号传导也可与死亡受体凋亡途径（Fas、TNF）、凋亡的细胞内调节因子JNK和p38丝裂原活化蛋白激酶、Akt、核因子κB以及由Bcl-2家族成员介导的线粒体凋亡途径协同作用。此外，TGF-β1参与氧化应激的产生以及阻止清除凋亡小体所需的炎症过程，这进一步证明了它整合到凋亡途径中。不同刺激之间的相互作用和平衡为TGF-β1信号在特定细胞中的促凋亡或抗凋亡输出提供了基础。
