Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution.
BACKGROUND
Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by steatosis and periportal and lobular inflammation. The molecular mechanisms involved in the anomalous behavior of liver cells have only partially been disclosed. Human Chitotriosidase (Chit) is a member of the chitinase family that it is mainly synthesized by activated macrophages. We investigated chitotriosidase gene expression in Kupffer cells to determine the potential implication of this enzyme in the inflammation and in the progression from uncomplicated steatosis to steatohepatitis with progressive fibrosis.


METHODS
Seventy-five liver biopsies from 40 subjects with NASH, 20 with simple steatosis, and 15 controls were used to detect CHIT expression, tumor necrosis factor-alpha (TNF-alpha), alpha-smooth muscle actin (alpha-SMA), and lipid peroxidation.


RESULTS
CHIT was expressed exclusively by Kupffer cells. The levels of CHIT expression were significantly higher in NASH patients than in simple steatosis patients and in the control group. In addition, we found that CHIT over-expression influenced hepatic stellate cells activation, as demonstrated by the significant correlation between CHIT and alpha-SMA expression in NASH patients. A significant correlation was observed also between CHIT, TNF-alpha and lipid peroxidation in both NASH and simple steatosis.


CONCLUSIONS
These results suggest that CHIT over-produced by Kupffer cells may contribute to the progression of hepatic fibrosis.
Malaguarnera
Lucia
L
Department of Biomedical Sciences, University of Udine, Udine, Italy.
Di Rosa
Michelino
M
Rosa
Michelino D
MD
Zambito
Anna M
AM
dell'Ombra
Nicola
N
Di Marco
Roberto
R
Marco
Roberto D
RD
Malaguarnera
Mariano
M
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001706:Biopsy; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006596:Hexosaminidases / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007728:Kupffer Cells / Q000201:enzymology* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000199:Actins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D006596:Hexosaminidases; C086400:chitotriosidase