STAT1、SOCS3和PIAS1在肝脏中的表达在慢性丙型肝炎患者治疗反应中的作用。
The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy.
作者信息
El-Saadany Sherif, Ziada Dina H, El Bassat Hanan, Farrag Wael, El-Serogy Hesham, Eid Manal, Abdallah Manal, Ghazy Medhat, Salem Hoda A
出版信息
Can J Gastroenterol. 2013 Feb;27(2):e13-7. doi: 10.1155/2013/562765.
BACKGROUND
The underlying mechanisms of hepatitis C virus (HCV) resistance to treatment are unknown. Signal transducers and activators of transcription (STAT) proteins play a critical role in antiviral defense.
OBJECTIVE
To explore some of the mechanisms of HCV resistance to interferon, the expression of STAT1 and its negative regulators, protein inhibitor of activated STAT (PIAS1) and suppressor of cytokine signalling (SOCS3), in liver tissues of both inteferon responders and nonresponders in chronic HCV patients.
METHODS
Sixty patients were divided into the following groups: group 1a comprised 38 treatment-responder chronic HCV patients; group 1b consisted of 22 treatment-nonresponder chronic HCV patients; and group 2 consisted of six control subjects. Liver biopsies were examined for histological scoring; STAT1, SOCS3 and PIAS1 expression was analyzed using Western blotting methods.
RESULTS
STAT1 expression in the liver tissue of patients in group 1 was significantly increased compared with group 2 patients (P=0.001), while no significant difference in expression was observed between group 1a and group 1b patients (P=0.747). However, phosphorylated STAT1 protein was expressed at a significantly higher level in liver tissue of patients in group 1a compared with patients in group 1b (P=0.001). Western blot analysis of PIAS1 and SOCS3 protein expression in liver tissues from groups 1 and 2 revealed significantly increased expression in group 1 compared with group 2 (P=0.001). In addition, PIAS1 and SOCS3 protein expression was significantly higher in the liver tissues of patients in group 1b compared with patients in group 1a.
CONCLUSION
Levels of STAT1 and⁄or the protein expression of its negative regulators, PIAS1 and SOCS3, may be a good predictor of response to therapy. These could be used as biomarkers that are easily detected by Western blotting or immunostaining during standard histopathological liver biopsy analysis.
背景
丙型肝炎病毒（HCV）耐药的潜在机制尚不清楚。信号转导和转录激活因子（STAT）蛋白在抗病毒防御中起关键作用。
目的
探讨慢性HCV患者中干扰素应答者和无应答者肝组织中STAT1及其负调节因子——活化STAT蛋白抑制剂（PIAS1）和细胞因子信号转导抑制因子（SOCS3）的表达，以探究HCV对干扰素耐药的部分机制。
方法
60例患者分为以下几组：1a组包括38例治疗应答的慢性HCV患者；1b组由22例治疗无应答的慢性HCV患者组成；2组由6例对照受试者组成。对肝活检组织进行组织学评分；采用蛋白质印迹法分析STAT1、SOCS3和PIAS1的表达。
结果
与2组患者相比，1组患者肝组织中STAT1表达显著增加（P = 0.001），而1a组和1b组患者之间的表达无显著差异（P = 0.747）。然而，与1b组患者相比，1a组患者肝组织中磷酸化STAT1蛋白的表达水平显著更高（P = 0.001）。对1组和2组肝组织中PIAS1和SOCS3蛋白表达的蛋白质印迹分析显示，与2组相比，1组表达显著增加（P = 0.001）。此外，与1a组患者相比，1b组患者肝组织中PIAS1和SOCS3蛋白表达显著更高。
结论
STAT1水平和/或其负调节因子PIAS 和SOCS3的蛋白表达可能是治疗反应的良好预测指标。这些可作为生物标志物，在标准肝组织病理活检分析过程中通过蛋白质印迹法或免疫染色轻松检测到。
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