The expression and secretion of vimentin in the progression of non-alcoholic steatohepatitis
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The pathogenesis of non-alcoholic steatohepatitis (NASH) is notfully understood. In the present study, both in vitro and in vivovimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) toHepG2 cells enhanced caspase-3 activity and vimentinexpression, respectively. The combined effects of bothtreatments on vimentin expression and caspase-3 activationappeared to be synergic. In contrast, blockade of caspase-3activity by zVADfmk resulted in a significant reduction ofcleaved vimentin and secreted vimentin into the culturesupernatant. Similarly, lipid accumulation and inflammationoccurred in mice fed a methionine-choline-deficient diet; thus,vimentin expression and serum cleaved vimentin levels wereincreased. However, vimentin was not significantly upregulated,and no cleavage occurred in mice fed a high-fat diet. It wasconclusively determined that lipid accumulation in hepatocytesinduces apoptosis through a caspase-3 dependent pathway;whereas, LPS stimulates vimentin expression, leading to itscleavage and secretion. Increased vimentin fragment levelsindicated the existence of substantial hepatocellular death via an apoptotic mechanism.
Abstract
The pathogenesis of non-alcoholic steatohepatitis (NASH) is notfully understood. In the present study, both in vitro and in vivovimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) toHepG2 cells enhanced caspase-3 activity and vimentinexpression, respectively. The combined effects of bothtreatments on vimentin expression and caspase-3 activationappeared to be synergic. In contrast, blockade of caspase-3activity by zVADfmk resulted in a significant reduction ofcleaved vimentin and secreted vimentin into the culturesupernatant. Similarly, lipid accumulation and inflammationoccurred in mice fed a methionine-choline-deficient diet; thus,vimentin expression and serum cleaved vimentin levels wereincreased. However, vimentin was not significantly upregulated,and no cleavage occurred in mice fed a high-fat diet. It wasconclusively determined that lipid accumulation in hepatocytesinduces apoptosis through a caspase-3 dependent pathway;whereas, LPS stimulates vimentin expression, leading to itscleavage and secretion. Increased vimentin fragment levelsindicated the existence of substantial hepatocellular death via an apoptotic mechanism.
참고문헌 (21)
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