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: Su Jin Lee, Jae Do Yoo, Soo Young Choi, Oh-Shin Kwon
• Journal: BMB reports (BMB Rep) Vol. 47 Issue 8 Pg. 457-62 (Aug 2014) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 24325816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Lipopolysaccharides
• Palmitates
• Vimentin
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• Caspase 3

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Diet
• Disease Models, Animal
• Disease Progression
• Hep G2 Cells
• Humans
• Lipopolysaccharides (toxicity)
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (metabolism, pathology)
• Palmitates (toxicity)
• Up-Regulation (drug effects)
• Vimentin (metabolism)