Differential role of Jak-STAT signaling in retinal degenerations
Differential role of Jak-STAT signaling in retinal degenerations
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DOI：
10.1096/fj.06-5895fje
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
Grimm, Christian
中科院分区：
文献类型：
--
作者：
Samardzija, Marijana;Wenzel, Andreas;Grimm, Christian
视网膜变性是严重视力障碍或失明的主要原因。了解潜在的分子机制是开发人类患者治疗方法的先决条件。我们在三种小鼠模型中显示，诱导和遗传性视网膜变性诱导 LIF 和 CLC 作为白细胞介素 (IL)-6 蛋白家族的成员，激活 Jak-STAT 信号通路的蛋白，并作为负反馈环上调细胞因子信号传导的抑制因子。在诱导性视网膜变性模型中抑制 Jak2 会导致光感受器受到保护，但在遗传性视网膜变性模型中则不会。 Akt 的差异激活表明不同模型中细胞死亡和/或存活的替代途径。光感受器变性期间诱导的蛋白质主要并不在光感受器中表达，而是在其他视网膜层的细胞中表达。这表明了一种模型，其中光感受器损伤向内视网膜细胞发出信号，进而启动反应以支持受损细胞的活力或加速死亡。
Retinal degeneration is a major cause of severe visual impairment or blindness. Understanding the underlying molecular mechanisms is a prerequisite to develop therapeutic approaches for human patients. We show in three mouse models that induced and inherited retinal degeneration induces LIF and CLC as members of the interleukin (IL)-6 family of proteins, activates proteins of the Jak-STAT signaling pathway, and up-regulates suppressors of cytokine signaling as a negative feedback loop. Inhibition of Jak2 leads to protection of photoreceptors in a model of induced but not in a model of inherited retinal degeneration. Differential activation of Akt suggests alternative pathways for cell death and/or survival in different models. Proteins induced during photoreceptor degeneration are not mainly expressed in photoreceptors but in cells of other retinal layers. This suggests a model in which photoreceptor injury is signaled to cells of the inner retina, which in turn initiate a response either to support viability or accelerate death of injured cells.