The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy.

IF 2.7 4区医学 Q2 Medicine

Canadian Journal of Gastroenterology Pub Date : 2013-02-01 DOI:10.1155/2013/562765

Sherif El-Saadany, Dina H Ziada, Hanan El Bassat, Wael Farrag, Hesham El-Serogy, Manal Eid, Manal Abdallah, Medhat Ghazy, Hoda A Salem

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引用次数: 18

Abstract

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.

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肝组织STAT1、SOCS3和PIAS1表达在慢性丙型肝炎患者治疗反应中的作用

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着关键作用。目的:探讨慢性丙型肝炎病毒对干扰素耐药的一些机制，以及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)和细胞因子信号抑制因子(SOCS3)的表达。方法:60例患者分为以下组:1a组包括38例治疗应答的慢性HCV患者;1b组包括22例治疗无效的慢性HCV患者;第二组为6名对照组。肝脏活检进行组织学评分;Western blotting法分析STAT1、SOCS3和PIAS1的表达。结果:1组患者肝组织中STAT1的表达较2组显著升高(P=0.001)，而1a组与1b组之间表达差异无统计学意义(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升高(P=0.001)。Western blot分析1组和2组肝组织中PIAS1和SOCS3蛋白的表达，结果显示1组与2组相比，PIAS1和SOCS3蛋白的表达显著升高(P=0.001)。此外，与1a组患者相比，1b组患者肝组织中PIAS1和SOCS3蛋白表达明显升高。结论:STAT1和/或其负调节因子PIAS1和SOCS3的蛋白表达水平可能是治疗反应的良好预测指标。这些可以作为生物标志物，在标准的组织病理学肝活检分析中很容易通过免疫印迹或免疫染色检测到。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Canadian Journal of Gastroenterology 医学-胃肠肝病学

CiteScore

4.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.