[Frontiers in Bioscience 16, 2794-2811, June 1, 2011]

JAK-STAT signaling in hepatic fibrosis

Markus Mair1, Leander Blaas1, Christoph H. Osterreicher2, Emilio Casanova1, Robert Eferl1,3

1Ludwig Boltzmann Institute for Cancer Research, Waehringer Strasse 13a, A-1090 Vienna, Austria, 2Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Waehringer Strasse 13a, A-1090 Vienna, Austria, 3Institute for Cancer Research, Medical University of Vienna (MUV), Borschkegasse 8, A-1090 Vienna, Austria

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Liver fibrosis and cirrhosis in humans
2.2. Chronic injury - fibrosis - cirrhosis - HCC axis
2.3. Cellular basis and molecular pathways in liver fibrosis
2.4. Genetic and chemical animal models for liver fibrosis
3. STATs in liver regeneration, cancer and physiology
3.1. STAT1
3.2. STAT2
3.3. STAT3
3.4. STAT4
3.5. STAT5
3.6. STAT6
4. STATs in hepatic fibrosis: focus on IL-6/gp130/STAT3
5. STATs in hepatic fibrosis: focus on GH/STAT5/IGF-1
6. Other STATs in liver fibrosis
7. Conclusions and perspectives
8. Acknowledgements
9. References

1. ABSTRACT

Chronic liver injury, liver fibrosis and formation of hepatocellular carcinoma are intimately linked and represent a major medical challenge since treatment options are limited. Therefore, it is important to identify cellular and molecular pathways that promote liver damage or provide hepatoprotection for development of therapeutic approaches. Recently, the transcription factors STAT3 and STAT5 have been implicated in liver fibrosis induced by cholestatic liver damage. In this review, we summarize our current knowledge about STAT proteins in liver fibrosis and focus on common activities that underlie the hepatoprotective mechanisms regulated by IL-6/gp130/STAT3 and GH/STAT5/IGF-1 signaling pathways.