Keratin intermediate filaments: a dynamic framework for major signaling molecules involved in epithelial cell survival and cell death

中间丝（if）与微管和肌动蛋白微丝是大多数哺乳动物细胞的主要细胞骨架成分。角蛋白是上皮细胞中表达的IF蛋白。为了阐明角蛋白8和角蛋白18在肝细胞（肝脏的上皮细胞）中的作用，一种基因靶向方法是必要的。例如，携带K8或K18突变的小鼠的肝细胞会破坏IF网络结构或影响其磷酸化模式，K8或K18缺失的小鼠极易受到肝毒性药物诱导的细胞凋亡。因此，K8/18在保护上皮细胞免受毒物应激诱导中发挥重要作用。K8/18实现其保护作用的机制还远未完全了解。

Intermediate filaments (IFs) are with microtubules and actin microfilaments the major cytoskeletal components of most mammalian cells. Keratins are the IF proteins that are expressed in epithelial cells. A gene-targeting approach has been necessary to unravel the roles of keratin 8 and 18 in hepatocytes, the epithelial cells of the liver. For instance, hepatocytes from mice carrying K8 or K18 mutations that disrupt IF network structure or affect their phosphorylation pattern, and K8- or K18-null mice are highly susceptible to apoptosis induced by hepatotoxic agents. Thus K8/18 are proposed to play an important role in the protection of epithelial cells against stress-induced by toxicants. The mechanisms by which K8/18 accomplish their protective role is far from being fully understood.