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Copyright ©2013 Baishideng Publishing Group Co.
World J Gastroenterol. Dec 21, 2013; 19(47): 8831-8849
Published online Dec 21, 2013. doi: 10.3748/wjg.v19.i47.8831
Table 2 Galectins in inflammation-associated liver injury
Galectin memberExperimental modelRoleEffectsRef.
Galectin-1Hepatitis induced by injection of Con AProtectivePrevents both liver injury and T-helper cell liver infiltration, induces apoptosis of Con A-activated T cells, suppresses plasma levels of TNF and IFN-γ[89]
Inflammation-induced chronic cholestatic hepatitis at an early age, and HCC at later age (Mdr2-KO mice)ProtectiveGalectin-1 is up-regulated in Mdr2-KO/B6 strain at early age[91]
Galectin-1-KO mice in the context of Con A-induced autoimmune hepatitisProtectiveCon A up-regulates galectin-1 in galectin-1-KO/B6 and Mdr2-KO/FVB strains. Endogenous galectin-1 selectively protects liver in the B6, but not in the FVB genetic background. It probably determines strain-specific differences in the course of chronic hepatitis and HCC development in the Mdr2-KO model[91]
Galectin-3NASH modelGalectin-3-KO miceProtectiveDevelops NAFLD/NASH spontaneously with aging[140,141]
CDAA diet-induced NAFLD/NASH in galectin-3-KO miceProtectiveGalectin-3 deficiency causes more severe hepatic injury and alterations in the expression of genes associated with carcinogenesis and lipid metabolism[142]
Atherogenic diet-induced NASH in galectin-3-KO micePromotes disease severityAttenuates NASH: inhibits HSC-driven fibrosis, reduces inflammatory-cell infiltration and hepatocyte apoptosis, acts as a major scavenger receptor involved in ALE/AGE uptake by the liver[143]
Human liver tissuesProtectiveNegative expression of galectin-3 in normal hepatocytes, strong staining for galectin-3 in hepatocytes from patients with steatosis hepatitis, hepatitis, cholestasis and cirrhosis[145]
Acute liver failure induced by APAP- hepatotoxicity in galectin-3-KO micePerpetuates liver injuryIn wild type mice, galectin-3 is up-regulated in liver infiltrating macrophages. In galectin-3 deficient mice the pro-inflammatory M1-type macrophages subpopulation, the classical macrophage activation markers iNOS, TNF and IL-12 and pro-inflammatory chemokines are reduced[147,148]
Hepatitis induced by injection of Con A in galectin-3-KO micePro-inflammatoryGalectin-3 deficiency reduces the number of T lymphocytes, B lymphocytes, dendritic cells, NK and NKT cells and enhances apoptosis of mononuclear cells[149]
Con A-induced liver injury in wild type mice pretreated with a selective inhibitor of galectin-3 (TD139)Pro-inflammatoryTD139 attenuates liver injury, reduces the number of CD4+ and CD8+ T cells, favors the influx of IL-10-producing CD4+ T cells in the liver, decreases serum levels of IFN-γ, IL-17 and IL-4[149]
Galectin-9Blockade of the TIM-3/galectin-9 pathway using an anti-TIM-3 or anti-galectin-9 mAb in a context of liver IRIProtectiveBlockade of the TIM-3/galectin-9 pathway increases hepatocellular damage, local neutrophil infiltration, T cell and macrophage accumulation and liver cell apoptosis. Increases IFN-γ production by Con A-stimulated spleen T cells and augmented TNF and IL-6 production by Con A-stimulated macrophages/T cells[190]
Single injection of galectin-9 in the murine model of liver injury induced by Con AProtectiveEliminates activated CD4+ effector T cells, prevents the synthesis and/or release of proinflammatory cytokine[191]
Mouse model of diet-induced NAFLD treated with galectin-9Limits the inflammatory responseInduces apoptosis of NKT cells, also interacts with TIM-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation[195]