Heat Shock Protein 27 is down-regulated in Ballooned Hepatocytes of Patients with Nonalcoholic Steatohepatitis (NASH)

Abstract

Ballooning degeneration (BD) of hepatocytes is a distinguishing histological feature associated with the progression of nonalcoholic fatty liver disease (NAFLD). Under the assumption that NAFLD severity is associated with metabolic stress we explored the hypothesis that heat shock 27 kDa protein 1 (HSP27),a protein chaperone involved in stress resistance and cytoskeletal remodeling, might be deregulated in ballooned hepatocytes. We observed that fasting plasma glucose (fpG) (p = 0.00002), total cholesterol (p = 0.02) and triglycerides (p = 0.01) levels, and female sex (p = 0.01) were significantly associated withthe presence of BD. A logistic regression model showed that BD was independently associated with fpG (p = 0.002); OR per unit of glucose concentration 1.05, 95% confidence interval 1.02?1.09. Furthermore, BD was associated with a significant 2.24-fold decrease in the expression level of HSP27-mRNA in comparison with the absence of ballooning, p = 0.002. Ballooned hepatocytes showed very low HSP27immunoreactivity compared with hepatocytes without ballooning (p = 0.009); HSP27 immunoreactivity was inversely correlated with fpG levels (R: −0.49, p = 0.01). In conclusion, BD is associated with downregulation of liver HSP27 gene and protein expression, suggesting that ballooned hepatocytes fail to ensure a robust physiological response to metabolic-induced stress.