Atorvastatin inhibits proliferation and apoptosis, but induces senescence in hepatic myofibroblasts and thereby attenuates hepatic fibrosis in rats

• Published in: Laboratory investigation Vol. 92; no. 10; pp. 1440 - 1450
• Main Authors: Klein, Sabine, Klösel, Jeremias, Schierwagen, Robert, Körner, Christian, Granzow, Michaela, Huss, Sebastian, Mazar, Irela Gretchen Reza, Weber, Susanne, van den Ven, Peter F M, Pieper-Fürst, Ursula, Fürst, Dieter O, Nattermann, Jacob, Lammert, Frank, Sauerbruch, Tilman, Trebicka, Jonel
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.10.2012; Nature Publishing Group US; Nature Publishing Group
• Subjects: 631/80/509; 631/92/609; 692/699/1503/1607/1605; Actins - immunology; Actins - metabolism; Aging - drug effects; Animals; Apoptosis - drug effects; Atorvastatin; beta-Galactosidase - analysis; beta-Galactosidase - metabolism; Biological and medical sciences; Biotechnology; Cell Proliferation - drug effects; Collagen - metabolism; Connective Tissue Growth Factor - genetics; Connective Tissue Growth Factor - metabolism; cytokines; Desmin - immunology; Desmin - metabolism; Dose-Response Relationship, Drug; fibrogenesis; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; hepatic stellate cells; Hepatic Stellate Cells - drug effects; Heptanoic Acids - pharmacology; HMG-CoA reductase inhibitor; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Laboratory Medicine; Liver - cytology; Liver - drug effects; Liver - metabolism; Liver Cirrhosis - drug therapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; myofibroblasts; Myofibroblasts - drug effects; Other diseases. Semiology; Pathology; Pyrroles - pharmacology; Rats; Rats, Sprague-Dawley; research-article; senescence; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; senescence; hepatic stellate cells; cytokines; fibrogenesis; myofibroblasts; HMG-CoA reductase inhibitor; Cell proliferation; Biotechnology; Senescence; Rat; Liver; Myofibroblast; Hepatic disease; Hypocholesterolemic agent; Clinical biology; Hepatic fibrosis; Digestive system; Enzyme; Rodentia; Cytokine; Enzyme inhibitor; Statin derivative; Kupffer cell; Vertebrata; Mammalia; Cell death; Animal; Atorvastatin; Digestive diseases; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Apoptosis; Antilipemic agent

Hepatic myofibroblasts (MFB) show increased proliferation, migration and collagen production, which are crucial for hepatic fibrogenesis. Atorvastatin treatment inhibits proliferation, apoptosis and cytokine production of MFB in bile duct-ligated (BDL) rats in vivo. Here, we have further investigate...