The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis

Weng, Hong-Lei; Liu, Yan; Chen, Jia-Lin; Huang, Tong; Xu, Li-Jun; Godoy, Patricio; Hu, Jun-Hua; Zhou, Cheng; Stickel, Felix; Marx, Alexander; Bohle, Rainer M; Zimmer, Vincent; Lammert, Frank; Mueller, Sebastian; Gigou, Michelle; Samuel, Didier; Mertens, Peter R; Singer, Manfred V; Seitz, Helmut K and Dooley, Steven (2009). The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis. Hepatology, 50(1), pp. 230-43. Hoboken, N.J.: Wiley Interscience 10.1002/hep.22934

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It is unknown whether transforming growth factor beta1 (TGF-beta1) 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-beta1 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-beta1 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 > or =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-beta1 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
UniBE Contributor:	Stickel, Felix
ISSN:	0270-9139
ISBN:	19441105
Publisher:	Wiley Interscience
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:07
Last Modified:	05 Dec 2022 14:20
Publisher DOI:	10.1002/hep.22934
PubMed ID:	19441105
Web of Science ID:	000267605500025
URI:	https://boris.unibe.ch/id/eprint/29579 (FactScience: 146662)