PTEN expression is down-regulated in liver tissues of rats with hepatic fibrosis induced by biliary stenosis

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2009-09, Vol.117 (9), p.681-691
• Main Authors: HAO, LI SEN, ZHANG, XIAO LAN, AN, JUN YAN, KARLIN, JUSTIN, TIAN, XIAO PENG, DUN, ZHI NA, XIE, SHU RUI, CHEN, SHUANG
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Base Sequence; Biological and medical sciences; Cell Proliferation; cirrhosis; Common Bile Duct; DNA Primers - genetics; Down-Regulation; Fundamental and applied biological sciences. Psychology; hepatic fibrosis; hepatic stellate cells; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - pathology; Infectious diseases; Ligation; Liver Cirrhosis, Experimental - etiology; Liver Cirrhosis, Experimental - genetics; Liver Cirrhosis, Experimental - metabolism; Liver Cirrhosis, Experimental - pathology; Male; Medical sciences; Microbiology; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2009.02515.x

The gene phosphatase and tensin homolog deleted on chromosome 10 (PTEN) codes for a tumor-suppressor phospholipid phosphatase. Deletion, mutation or abnormal expression of PTEN is commonly found in many kinds of malignant tumors. At the time of this study, though, the role of PTEN expression in the pathology of hepatic fibrosis remains unclear. In this study, we investigate the dynamic expression of PTEN in a rat model of hepatic fibrosis, with special emphasis on the activation and proliferation of hepatic stellate cells (HSC) in vivo. The rat model of hepatic fibrosis used in this study employed common bile duct ligation. At four time points, the expression of PTEN in hepatic tissues and activated HSC in rat liver tissues was measured by immunohistochemical staining, Western blotting, real-time fluorescent quantitative PCR and immunofluorescence confocal laser scanning microscopy, respectively. Further, α-smooth muscle actin (α-SMA), an activated HSC marker in rat liver tissues, was detected by immunohistochemical staining. This study showed that aggravation of hepatic fibrosis led to gradually decreasing expression of PTEN in the hepatic tissues. Further, as hepatic fibrosis worsens, PTEN-expressing activated HSC accounts for an increasingly smaller percentage of all activated HSC. In contrast, the percentage of α-SMA-expressing HSC cells increases significantly. In conclusion, expression of PTEN mRNA and protein is down-regulated in fibrogenic rat liver tissue, and its expression in HSC in vivo also decreases with progression of fibrosis. Thus, these results show that the dynamic expression of PTEN in hepatic tissues negatively correlates with activation and proliferation of HSC.