title: The expression and secretion of vimentin in the progression of non-alcoholic steatohepatitis.
abstract: The pathogenesis of non-alcoholic steatohepatitis (NASH) is not fully understood. In the present study, both in vitro and in vivo vimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) to HepG2 cells enhanced caspase-3 activity and vimentin expression, respectively. The combined effects of both treatments on vimentin expression and caspase-3 activation appeared to be synergic. In contrast, blockade of caspase-3 activity by zVADfmk resulted in a significant reduction of cleaved vimentin and secreted vimentin into the culture supernatant. Similarly, lipid accumulation and inflammation occurred in mice fed a methionine-choline-deficient diet; thus, vimentin expression and serum cleaved vimentin levels were increased. However, vimentin was not significantly upregulated, and no cleavage occurred in mice fed a high-fat diet. It was conclusively determined that lipid accumulation in hepatocytes induces apoptosis through a caspase-3 dependent pathway; whereas, LPS stimulates vimentin expression, leading to its cleavage and secretion. Increased vimentin fragment levels indicated the existence of substantial hepatocellular death via an apoptotic mechanism.
authors: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
authors: Su Jin
authors: SJ
authors: Lee
authors: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
authors: Jae Do
authors: JD
authors: Yoo
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors: Soo Young
authors: SY
authors: Choi
authors: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.
authors: Oh-Shin
authors: OS
authors: Kwon
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D018450:Disease Progression; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology*; D010168:Palmitates / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D008070:Lipopolysaccharides; D010168:Palmitates; D014746:Vimentin; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D053148:Caspase 3