Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.
The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease.
Fillon
Sophie
S
Department for Physiology, University of Tübingen, Gmelinstrasse 5, D-72076 Tübingen, Germany.
Klingel
Karin
K
Wärntges
Simone
S
Sauter
Martina
M
Gabrysch
Sabine
S
Pestel
Sabine
S
Tanneur
Valerie
V
Waldegger
Siegfried
S
Zipfel
Annette
A
Viebahn
Richard
R
Häussinger
Dieter
D
Bröer
Stefan
S
Kandolf
Reinhard
R
Lang
Florian
F
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D005353:Fibronectins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006509:Hepatitis B / Q000378:metabolism / Q000473:pathology; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology; D006525:Hepatitis, Viral, Human / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017874:Immediate-Early Proteins; D017403:In Situ Hybridization; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D000099184:Serum-Glucocorticoid Regulated Kinases
D005353:Fibronectins; D006861:Hydrogen Peroxide; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D016877:Oxidants; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000099184:Serum-Glucocorticoid Regulated Kinases