The Etiology of Liver Damage Imparts Cytokines Transforming Growth Factor β1 or Interleukin-13 as Driving Forces in Fibrogenesis

被引：110

作者：

Weng, Hong-Lei ^{[1
,5
]}

Liu, Yan

Chen, Jia-Lin ^{[6
]}

Huang, Tong ^{[7
]}

Xu, Li-Jun ^{[8
]}

Godoy, Patricio

Hu, Jun-Hua

Zhou, Cheng ^{[5
]}

Stickel, Felix ^{[9
]}

Marx, Alexander ^{[2
]}

Bohle, Rainer M. ^{[10
]}

Zimmer, Vincent ^{[11
]}

Lammert, Frank ^{[11
]}

Mueller, Sebastian ^{[3
,4
]}

Gigou, Michelle ^{[12
]}

Samuel, Didier ^{[12
]}

Mertens, Peter R. ^{[13
]}

Singer, Manfred V.

Seitz, Helmut K. ^{[3
,4
]}

Dooley, Steven

机构：

[1] Heidelberg Univ, Fac Med, Dept Med 2, D-68167 Mannheim, Germany

[2] Heidelberg Univ, Fac Med Mannheim, Dept Pathol, D-68167 Mannheim, Germany

[3] Heidelberg Univ, Salem Med Ctr, Dept Med, D-68167 Mannheim, Germany

[4] Heidelberg Univ, Salem Med Ctr, Lab Alcohol Res Liver Dis & Nutr, D-68167 Mannheim, Germany

[5] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Inst Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China

[6] First Hosp Jianxing, Coll Jiaxing, Dept Pathol, Jiaxing, Peoples R China

[7] Zhenhai Lianhua Hosp, Dept Internal Med, Ningbo, Peoples R China

[8] Fujian Med Univ, Fuzhou Infect Dis Hosp, Inst Liver Dis, Fuzhou, Peoples R China

[9] Univ Bern, Inst Clin Pharmacol, Bern, Switzerland

[10] Univ Saarland, Inst Pathol, D-6650 Homburg, Germany

[11] Univ Saarland, Dept Internal Med 2, D-6650 Homburg, Germany

[12] INSERM, Villejuif, France

[13] Otto VonGuericke Univ Magdegurg, Dept Hypertens & Nephrol, D-39016 Magdeburg, Germany

来源：

HEPATOLOGY | 2009年 / 50卷 / 01期

关键词：

SCHISTOSOMA-MANSONI INFECTION; C-VIRUS CORE; HEPATITIS-C; TGF-BETA; TISSUE FIBROSIS; IL-13; EXPRESSION; RAT; GROWTH-FACTOR-BETA-1; CELLS;

D O I：

10.1002/hep.22934

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

It is unknown whether transforming growth factor beta 1 (TGF-beta 1) signaling uniformly participates in fibrogenic chronic liver diseases, irrespective of the underlying origin, or if other cytokines such as interleukin (IL)-13 share in fibrogenesis (e.g., due to regulatory effects on type I pro-collagen expression). TGF-beta 1 signaling events were scored in 396 liver tissue samples from patients with diverse chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), Schistosoma japonicum infection, and steatosis/steatohepatitis. Phospho-Smad2 staining correlated significantly with fibrotic stage in patients with HBV infection (n = 112, P < 0.001) and steatosis/steatohepatitis (n = 120, P < 0.01), but not in patients with HCV infection (n = 77, P > 0.05). In tissue with HBx protein expression, phospho-Smad2 was detectable, suggesting a functional link between viral protein expression and TGF-beta 1 signaling. For IL-13, immunostaining correlated with fibrotic stage in patients with HCV infection. and steatosis/steatohepatitis. IL-13 protein was more abundant in liver tissue lysates from three HCV patients compared with controls, as were IL-13 serum levels in 68 patients with chronic HCV infection compared with 20 healthy volunteers (72.87 +/- 26.38 versus 45.41 +/- 3.73, P < 0.001). Immunohistochemistry results suggest that IL-13-mediated liver fibrogenesis may take place in the absence of phospho-signal transducer and activator of transcription protein 6 signaling. In a subgroup of patients with advanced liver fibrosis (stage >= 3), neither TGF-beta nor IL-13 signaling was detectable. Conclusion: Depending on the cause of liver damage, a predominance of TGF-beta or IL-13 signaling is found. TGF-beta 1 predominance is detected in HBV-related liver fibrogenesis and IL-13 predominance in chronic HCV infection. In some instances, the underlying fibrogenic mediator remains enigmatic. (HEPATOLOGY 2009;50:230-243.)

引用

页码：230 / 243

页数：14

共 45 条

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