Core-fucose-specific Pholiota squarrosa lectin decreased hepatic inflammatory macrophage infiltration in steatohepatitis mice.

Autor: Kamada, Yoshihiro, Ueda, Yui, Matsuno, Eriko, Matsumoto, Riku, Akita, Maaya, Takamatsu, Shinji, Miyoshi, Eiji
Zdroj: Glycoconjugate Journal; Oct2024, Vol. 41 Issue 4/5, p267-278, 12p
Abstrakt: Recent findings in glycobiology revealed direct evidence of the involvement of oligosaccharide changes in human diseases, including liver diseases. Fucosylation describes the attachment of a fucose residue to a glycan or glycolipid. We demonstrated that fucosylated proteins are useful serum biomarkers for nonalcoholic fatty liver disease. Among fucosyltransferases, expression of alpha-1, 6-fucosyltransferase (Fut8), which produces core fucose, is frequently elevated during the progression of human chronic liver diseases. Previously, we discovered core-fucose-specific Pholiota squarrosa lectin (PhoSL) from Japanese mushroom Sugitake. Lectins are bioactive compounds that bind to glycan specifically, and various kinds of lectin have a variety of biological functions. Using high-fat and high-cholesterol (HFHC)–fed steatohepatitic mice, we found that core fucosylation increases in hepatic inflammatory macrophages. Antibody drugs bind to specific antigens and block protein function. We hypothesized that, like antibody drugs, PhoSL could have inhibitory effects on glycoproteins involved in steatohepatitis progression. PhoSL administration dramatically decreased hepatic macrophage infiltration and liver fibrosis–related gene expression. Using mouse macrophage-like cell RAW264.7, we found that PhoSL enhanced core-fucose-mediated activation of macrophage cell death by blocking interferon-γ/signal transducer and activator of transcription 1 (STAT1) signaling. Core-fucose-mediated cell death is a mechanism for the anti-inflammatory effects and anti-fibrotic effects of PhoSL on activated macrophages in steatohepatitic liver. In addition, PhoSL provides an anti-fibrotic effect by blocking transforming growth factor-β/SMAD family member 3 signaling in hepatic stellate cells. In conclusion, we found core-fucose-specific PhoSL administration could suppress steatohepatitis progression by decreasing inflammatory macrophage infiltration and fibrotic signaling in hepatic stellate cells. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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