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首页> 外文期刊>Molecular biology of the cell >Reg-II is an exocrine pancreas injury-response product that is up-regulated by keratin absence or mutation
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Reg-II is an exocrine pancreas injury-response product that is up-regulated by keratin absence or mutation

机译：Reg-II是一种外分泌胰腺损伤反应产物，可通过缺少角蛋白或突变来上调

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The major keratins in the pancreas and liver are keratins 8 and 18 (K8/K18), but their function seemingly differs in that liver K8/K18 are essential cytoprotective proteins, whereas pancreatic K8/K18 are dispensable. This functional dichotomy raises the hypothesis that K8-null pancreata may undergo compensatory cytoprotective gene expression. We tested this hypothesis by comparing the gene expression profile in pancreata of wild-type and K8-null mice. Most prominent among the up-regulated genes in K8-null pancreas was mRNA for regenerating islet-derived (Reg)-II, which was confirmed by quantitative reverse transcription-polymerase chain reaction and by an anti-Reg-II peptide antibody we generated. Both K8-null and wild-type mice express Reg-II predominantly in acinar cells as determined by in situ hybridization and immunostaining. Analysis of Reg-II expression in various keratin-related transgenic mouse models showed that its induction also occurs in response to keratin cytoplasmic filament collapse, absence, or ablation of K18 Ser52 but not Ser33 phosphorylation via Ser-to-Ala mutation, which represent situations associated with predisposition to liver but not pancreatic injury. In wild-type mice, Reg-II is markedly up-regulated in two established pancreatitis models in response to injury and during the recovery phase. Thus, Reg-II is a likely mouse exocrine pancreas cytoprotective candidate protein whose expression is regulated by keratin filament organization and phosphorylation.
机译：胰腺和肝脏中的主要角蛋白是角蛋白8和18（K8 / K18），但是它们的功能似乎有所不同，因为肝脏K8 / K18是必需的细胞保护蛋白，而胰腺K8 / K18是可有可无的。这种功能性的二分法提出了这样的假设，即K8-无效胰腺可能经历代偿性细胞保护基因表达。我们通过比较野生型和K8型小鼠胰腺中的基因表达谱，检验了这一假设。在K8无效胰腺中上调基因中最突出的是用于再生胰岛衍生（Reg）-II的mRNA，这已通过定量逆转录聚合酶链反应和我们产生的抗Reg-II肽抗体得以证实。通过原位杂交和免疫染色确定，K8空小鼠和野生型小鼠均主要在腺泡细胞中表达Reg-II。在各种与角蛋白相关的转基因小鼠模型中Reg-II表达的分析表明，其诱导也响应于角蛋白胞质细丝的塌陷，不存在或被K18 Ser52消融而发生，而不是通过Ser-to-Ala突变引起的Ser33磷酸化，这代表了情况与肝脏易感性有关，但与胰腺损伤无关。在野生型小鼠中，Reg-II在两种建立的胰腺炎模型中均显着上调，以响应损伤和恢复阶段。因此，Reg-II是一种可能的小鼠外分泌胰腺细胞保护候选蛋白，其表达受角蛋白丝组织和磷酸化的调节。

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