Zhong Bihui, Zhou Qin, Toivola Diana M, Tao Guo-Zhong, Resurreccion Evelyn Z, Omary M Bishr
VA Palo Alto Health Care System, Department of Medicine, 3801 Miranda Avenue, 154J, Palo Alto, CA 94304, USA.
J Cell Sci. 2004 Apr 1;117(Pt 9):1709-19. doi: 10.1242/jcs.01016.
Keratin polypeptides 8 and 18 (K8/K18) are the major intermediate filament proteins of pancreatic acinar cells and hepatocytes. Pancreatic keratin function is unknown, whereas hepatocyte keratins protect from mechanical and non-mechanical forms of stress. We characterized steady-state pancreatic keratin expression in Balb/c mice after caerulein and choline-deficient ethionine-supplemented diet (CDD), or on exposure to the generalized stresses of heat and water immersion. Keratins were studied at the protein, RNA and organizational levels. Isolated acini were used to study the role of nuclear factor (NF)-kappaB using selective inhibitors. Keratins were found to be abundant proteins making up 0.2%, 0.3% and 0.5% of the total cellular protein of pancreas, liver and small intestine, respectively. Caerulein and CDD caused a threefold transcription-mediated overall increase in K8/K18/K19/K20 proteins. Keratin overexpression begins on tissue recovery, peaks 2 days after caerulein injection, or 1 day after CDD discontinuation, and returns to basal levels after 10 days. K19/K20-containing cytoplasmic filaments are nearly absent pre-injury but form post-injury then return to their original membrane-proximal distribution after 10 days. By contrast, generalized stresses of heat or water-immersion stress do not alter keratin expression levels. Caerulein-induced keratin overexpression is associated with NF-kappaB activation when tested using ex vivo acinar cell cultures. In conclusion, keratins are abundant proteins that can behave as stress proteins in response to tissue-specific but not generalized forms of injury. Pancreatic keratin overexpression is associated with NF-kappaB activation and may serve unique functions in acinar or ductal cell response to injury.
角蛋白多肽8和18（K8/K18）是胰腺腺泡细胞和肝细胞中的主要中间丝蛋白。胰腺角蛋白的功能尚不清楚，而肝细胞角蛋白可保护细胞免受机械和非机械形式的应激。我们对用蛙皮素和胆碱缺乏的乙硫氨酸补充饮食（CDD）处理后的Balb/c小鼠，或暴露于热和水浸等全身性应激后的胰腺角蛋白稳态表达进行了表征。在蛋白质、RNA和组织水平上对角蛋白进行了研究。使用选择性抑制剂，利用分离的腺泡研究核因子（NF）-κB的作用。结果发现角蛋白是丰富的蛋白质，分别占胰腺、肝脏和小肠总细胞蛋白的0.2%、0.3%和0.5%。蛙皮素和CDD导致K8/K18/K19/K20蛋白在转录介导下总体增加了三倍。角蛋白的过表达在组织恢复时开始，在注射蛙皮素后2天或停止CDD饮食后1天达到峰值，并在10天后恢复到基础水平。含K19/K20的细胞质细丝在损伤前几乎不存在，但在损伤后形成，然后在10天后恢复到原来的膜近端分布。相比之下，热或水浸应激等全身性应激不会改变角蛋白的表达水平。当使用离体腺泡细胞培养进行测试时，蛙皮素诱导的角蛋白过表达与NF-κB激活有关。总之，角蛋白是丰富的蛋白质，可作为应激蛋白响应组织特异性而非全身性损伤形式。胰腺角蛋白过表达与NF-κB激活有关，可能在腺泡或导管细胞对损伤的反应中发挥独特作用。
