SERPINB3 modulates TGF-β expression in chronic liver disease

被引：42
|
作者：
Turato, Cristian [2 ]
Calabrese, Fiorella [3 ]
Biasiolo, Alessandra [1 ]
Quarta, Santina [1 ]
Ruvoletto, Mariagrazia [1 ]
Tono, Natascia [2 ]
Paccagnella, Daniela [4 ]
Fassina, Giorgio [5 ]
Merkel, Carlo [1 ]
Harrison, Tim J. [6 ]
Gatta, Angelo [1 ]
Pontisso, Patrizia [1 ]
机构：
[1] Univ Padua, Dept Clin & Expt Med, I-35128 Padua, Italy
[2] IRCCS, IOV, Padua, Italy
[3] Univ Padua, Dept Diagnost Med Sci & Special Therapies, Padua, Italy
[4] S Antonio Hosp, Operat Echog Unit, Padua, Italy
[5] Xeptagen SpA, Marghera, VE, Italy
[6] UCL Med Sch, Div Med, London, England
来源：
LABORATORY INVESTIGATION | 2010年 / 90卷 / 07期
关键词：
liver fibrosis; cirrhosis; cytokines; SERPINB3 reactive site loop; CELL CARCINOMA ANTIGEN; GROWTH-FACTOR-BETA; IDIOPATHIC PULMONARY-FIBROSIS; HEPATITIS-B-VIRUS; II RECEPTOR; TISSUE; OVEREXPRESSION; TRANSCRIPTION; FIBROBLASTS; BIOMARKERS;
D O I：
10.1038/labinvest.2010.55
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Transforming growth factor-beta 1 (TGF-beta 1) is the master cytokine in the pathogenesis of liver fibrosis. TGF-beta 1 and extent of fibrosis were correlated recently to the serpin SERPINB3 in idiopathic pulmonary fibrosis, a chronic disease recalling liver cirrhosis. The aim of this study was to assess the relation between SERPINB3, TGF-beta 1 and fibrosis in chronic liver diseases and to determine the effect of this serpin on TGF-beta 1 expression using in vitro models. SERPINB3 and TGF-beta 1 were evaluated in liver biopsies of 94 patients with chronic liver disease. The effect of SERPINB3 on TGF-beta 1 expression was determined in primary human hepatocytes, HepG2 and Huh7 cells transfected with intact SERPINB3 human gene or with reactive site loop deleted mutants. A significant correlation between TGF-beta 1 and SERPINB3 at the protein level was observed in liver biopsies, confirmed by a positive correlation at mRNA level. Both proteins were correlated to the extent of liver fibrosis. All transfected cells showed increased TGF-beta 1 mRNA and protein production and the integrity of the reactive site loop of the serpin was crucial to achieve this effect. In conclusion, chronically damaged hepatocytes produce SERPINB3 and TGF-beta, and the anti-protease activity of this serpin might be implicated in TGF-beta 1 induction. Laboratory Investigation (2010) 90, 1016-1023; doi: 10.1038/labinvest.2010.55; published online 8 March 2010
引用
收藏
页码：1016 / 1023
页数：8
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