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Keratin intermediate filaments in the colon: guardians of epithelial homeostasis
The International Journal of Biochemistry & Cell Biology ( IF 3.4 ) Pub Date : 2020-11-02 , DOI: 10.1016/j.biocel.2020.105878
Lauri Polari 1 , Catharina M Alam 1 , Joel H Nyström 1 , Taina Heikkilä 1 , Mina Tayyab 1 , Sarah Baghestani 1 , Diana M Toivola 2
Affiliation  

Keratin intermediate filament proteins are major cytoskeletal components of the mammalian simple layered columnar epithelium in the gastrointestinal tract. Human colon crypt epithelial cells express keratins 18, 19 and 20 as the major type I keratins, and keratin 8 as the type II keratin. Keratin expression patterns vary between species, and mouse colonocytes express keratin 7 as a second type II keratin. Colonic keratin patterns change during cell differentiation, such that K20 increases in the more differentiated crypt cells closer to the central lumen. Keratins provide a structural and mechanical scaffold to support cellular stability, integrity and stress protection in this rapidly regenerating tissue. They participate in central colonocyte processes including barrier function, ion transport, differentiation, proliferation and inflammatory signaling. The cell-specific keratin compositions in different epithelial tissues has allowed for the utilization of keratin-based diagnostic methods. Since the keratin expression pattern in tumors often resembles that in the primary tissue, it can be used to recognize metastases of colonic origin. This review focuses on recent findings on the biological functions of mammalian colon epithelial keratins obtained from pivotal in vivo models. We also discuss the diagnostic value of keratins in chronic colonic disease and known keratin alterations in colon pathologies. This review describes the biochemical properties of keratins and their molecular actions in colonic epithelial cells and highlights diagnostic data in colorectal cancer and inflammatory bowel disease patients, which may facilitate the recognition of disease subtypes and the establishment of personal therapies in the future.



中文翻译:

结肠中的角蛋白中间丝:上皮稳态的守护者

角蛋白中间丝蛋白是哺乳动物胃肠道中简单层状柱状上皮的主要细胞骨架成分。人结肠隐窝上皮细胞将角蛋白 18、19 和 20 表达为主要的 I 型角蛋白,将角蛋白 8 表达为 II 型角蛋白。角蛋白表达模式因物种而异,小鼠结肠细胞表达角蛋白 7 作为第二种 II 型角蛋白。结肠角蛋白模式在细胞分化过程中发生变化,因此 K20 在更接近中央管腔的分化程度更高的隐窝细胞中增加。角蛋白提供结构和机械支架,以支持这种快速再生组织中的细胞稳定性、完整性和压力保护。它们参与中央结肠细胞过程,包括屏障功能、离子转运、分化、增殖和炎症信号。不同上皮组织中的细胞特异性角蛋白组合物允许利用基于角蛋白的诊断方法。由于肿瘤中的角蛋白表达模式通常与原发组织中的相似,因此可用于识别结肠来源的转移瘤。本综述侧重于最近关于哺乳动物结肠上皮角蛋白的生物学功能的发现,这些角蛋白来自关键的体内模型。我们还讨论了角蛋白在慢性结肠疾病中的诊断价值和结肠病理中已知的角蛋白改变。这篇综述描述了角蛋白的生化特性及其在结肠上皮细胞中的分子作用,并重点介绍了结直肠癌和炎症性肠病患者的诊断数据,这可能有助于未来疾病亚型的识别和个人治疗的建立。

更新日期:2020-11-13
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