TY - JOUR
T1 - Deficiency in galectin-3 promotes hepatic injury in CDAA diet-induced nonalcoholic fatty liver disease
AU - Nomoto, Kazuhiro
AU - Nishida, Takeshi
AU - Nakanishi, Yuko
AU - Fujimoto, Makoto
AU - Takasaki, Ichiro
AU - Tabuchi, Yoshiaki
AU - Tsuneyama, Koichi
PY - 2012
Y1 - 2012
N2 - Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a -galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal 3 -/-) mice and wild-type (gal 3 +/+) mice with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in the gal 3 - / - male mice, as compared to the gal 3 + / + mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.
AB - Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a -galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal 3 -/-) mice and wild-type (gal 3 +/+) mice with choline-deficient L-amino-acid-defined (CDAA) diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in the gal 3 - / - male mice, as compared to the gal 3 + / + mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.
UR - http://www.scopus.com/inward/record.url?scp=84861065515&partnerID=8YFLogxK
U2 - 10.1100/2012/959824
DO - 10.1100/2012/959824
M3 - 学術論文
C2 - 22593713
AN - SCOPUS:84861065515
SN - 2356-6140
VL - 2012
JO - Scientific World Journal
JF - Scientific World Journal
M1 - 959824
ER -