角蛋白 18 磷酸化作为慢性乙型肝炎进展的标志物。
Keratin 18 phosphorylation as a progression marker of chronic hepatitis B.
机构信息
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
出版信息
Virol J. 2010 Mar 24;7:70. doi: 10.1186/1743-422X-7-70.
BACKGROUND
The intermediate filament proteins keratins 18 (K18) and 8 (K8) polymerize to form the cytoskeletal network in the mature hepatocytes. It has been shown that the phosphorylation of K18 at two serine residues, 33 and 52, correlates with the progression of hepatitis C, but little is known of chronic hepatitis B (CHB). In this study, we examined K18 phosphorylation in relation to CHB.
RESULTS
Site-specific phosphorylation of K18 was determined in livers of twelve healthy donors, and non-cirrhosis (n = 40) and cirrhosis (n = 21) patients. On average, progressively higher level of Ser52 phosphorylation was observed in non-cirrhotic and cirrhotic livers, while elevated Ser33 phosphorylation was detected in both livers but no significant difference. Progressive increase of Ser33 and Ser52 phosphorylation correlated with the elevation of both histological lesions and enzymatic activities of alanine aminotransferase in non-cirrhotic livers. In the hepatocytes of an inactive HBV carrier, strong signals of Ser33 phosphorylation were co-localized with viral infection, while only basal level of Ser52 phosphorylation was detected in infected cells.
CONCLUSION
Assuming all obtained data, our data suggest that K18 phosphorylation is a progression marker for CHB.
背景
中间丝蛋白角蛋白 18（K18）和 8（K8）聚合形成成熟肝细胞中的细胞骨架网络。已经表明，K18 在两个丝氨酸残基 33 和 52 处的磷酸化与丙型肝炎的进展相关，但对慢性乙型肝炎（CHB）知之甚少。在这项研究中，我们研究了 K18 磷酸化与 CHB 的关系。
结果
在 12 名健康供体的肝脏中以及非肝硬化（n = 40）和肝硬化（n = 21）患者中确定了 K18 的位点特异性磷酸化。平均而言，在非肝硬化和肝硬化肝脏中观察到 Ser52 磷酸化水平逐渐升高，而 Ser33 磷酸化在两种肝脏中均被检测到，但无显著差异。Ser33 和 Ser52 磷酸化的逐渐增加与非肝硬化肝脏中组织学病变和丙氨酸氨基转移酶酶活性的升高相关。在乙型肝炎病毒携带者的肝细胞中，Ser33 磷酸化的强信号与病毒感染共定位，而感染细胞中仅检测到基础水平的 Ser52 磷酸化。
结论
假设所有获得的数据，我们的数据表明 K18 磷酸化是 CHB 的进展标志物。
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