Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation downregulated in the regenerating liver

• Published in: World journal of gastroenterology : WJG Vol. 12; no. 47; pp. 7621 - 7625
• Main Authors: Xu, Cui-Ping, Ji, Wen-Min, van den Brink, Gijs R, Peppelenbosch, Maikel P
• Format: Journal Article
• Language: English
• Published: United States Department of Digestive Diseases,First Clinical College, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China%Department of Gastroenterology & Hepatology, Leiden University Medical Center, Leiden,The Netherlands%Department of Cell Biology, Faculty of Medical Sciences, University of Groningen, Groningen,The Netherlands 21.12.2006; Baishideng Publishing Group Co., Limited
• Subjects: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - metabolism; Bone Morphogenetic Proteins - pharmacology; Carcinoma, Hepatocellular; Cell Division - drug effects; Cell Division - physiology; Cell Line, Tumor; Down-Regulation - drug effects; Down-Regulation - physiology; Hepatocytes - cytology; Hepatocytes - metabolism; Humans; Liver Cancer; Liver Neoplasms; Liver Regeneration - physiology; Male; Rats; Rats, Wistar; Transforming Growth Factor beta - metabolism; Transforming Growth Factor beta - pharmacology; 细胞增殖; 肝切除术; Bone morphogenetic protein-2; Hepatocellular cardnoma; Partial hepatectomy; Liver regeneration
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v12.i47.7621

AIM： To characterize the expression and dynamic changes of bone morphogenetic protein （BMP）-2 in hepatocytes in the regenerating liver in rats after partial hepatectomy （PH）, and examine the effects of BMP-2 on proliferation of human Huh7 hepatoma cells. METHODS： Fifty-four adult male Wistar rats were randomly divided into three groups： A normal control （NC） group, a partial hepatectomized （PH） group and a sham operated （SO） group. To study the effect of liver regeneration on BMP-2 expression, rats were sacrificed before and at different time points after PH or the sham intervention （6, 12, 24 and 48 h）. For each time point, six rats were used in parallel. Expression and distribution of BMP-2 protein were determined in regenerating liver tissue by Western blot analysis and immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7 hepatoma cell line were assessed using an MTT assay. RESULTS： In the normal liver strong BMP-2 expression was observed around the central and portal veins. The expression of BMP-2 decreased rapidly as measured by both immunohistochemistry and Western blot analysis. This decrease was at a maximum of 3.22 fold after 12 h and returned to normal levels at 48 h after PH. No significant changes in BMP-2 immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced Huh7 cell proliferation. CONCLUSION： BMP-2 is expressed in normal adult rat liver and negatively regulates hepatocyte proliferation. The observed down regulation of BMP-2 following partial hepatectomy suggests that such down regulation may be necessary for hepatocyte proliferation.