Hironobu Fujii

Core fucosylation, catalyzed by α-1,6 fucosyltransferase (FUT8), regulates growth factor receptors in immune function. Although core fucose regulates many immune cell types, few reports confront the association between core fucose activity and an innate immune reaction. Here, we have investigated the function of core fucose in macrophages in vivo a...

Background: Many reports indicate that a high-serum trough level of anti-tumor necrosis factor (TNF) agents is required for sustained remission in patients with Crohn's disease The pharmacokinetics of anti-TNF agents in inflamed intestinal tissue, however, is not well investigated. We investigated the association between the tissue concentration o...

Oligosaccharide modifications play an essential role in various inflammatory diseases and cancers, but their pathophysiologic roles, especially in inflammation, are not clear. Inflammatory bowel disease (IBD) is an intractable chronic inflammatory disorder with an unknown aetiology, and the number of patients with IBD is increasing throughout the w...

Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing ?1-6 branching in asparagines-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabo...

Aim: We identified Mac-2 (galectin-3) binding protein (Mac-2 bp) as a novel diagnostic and liver fibrosis predicting biomarker for nonalcoholic steatohepatitis (NASH) in humans. In mouse models, there are no serum biomarkers predicting liver disease severity. In this study, we developed a mouse Mac-2 bp enzyme-linked immunosorbent assay (ELISA) sy...

Aim: To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis. Methods: Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked im...

Background & aims: Attachment of a fucose molecule to the innermost N-glycan in a glycoprotein (core fucosylation) regulates the activity of many growth factor receptors and adhesion molecules. The process is catalyzed by α1-6 fucosyltransferase (FUT8) and required for immune regulation, but it is not clear whether this process is dysregulated dur...

Background/objectives: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all malignancies, and its diagnosis in early stages is the most important prognostic factor. Chronic pancreatitis (CP), a common background of PDAC occurrence, is morphologically defined as progressive pancreatic fibrosis and inflammation accompanied by pancr...

The intestine is one of the most important organs associated with the immune system. It is thought that disruption of intestinal immunity causes inflammatory bowel disease (IBD). Recent advances in immune glyco-biology have provided novel insights into many human diseases. For example, studies of glycosylation remodeling in mice have underscored th...

Background: Oligosaccharide structures and their alterations have important roles in modulating intestinal inflammation. N-Acetylglucosaminyltransferase V (GnT-V) is involved in the biosynthesis of N-acetylglucosamine (GlcNAc) by β1,6-branching on N-glycans and is induced in various pathologic processes, such as inflammation and regeneration. GnT-...

Patients with inflammatory bowel disease (IBD) often exhibit vitamin K deficiency. Vitamin K has been shown to inhibit inflammation via interleukin (IL)-6 suppression. This study aimed to evaluate the effect of vitamin K in a murine model of colitis. Colitis was induced using dextran sulfate sodium (DSS) in mice fed either a vitamin K-deficient (K-...

Conclusion: The combination of serum Fuc-Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy. (Hepatology 2015).

AimGlycosylation changes induce various types of biological phenomena in human diseases. N-Acetylglucosaminyltransferase V (GnT-V) is one of the most important glycosyltransferases involved in cancer biology. Recently, many researchers have challenged studies of lipid metabolism in cancer. To elucidate the relationships between cancer and lipid met...

N‑Acetylglucosaminyltransferase V (GnT‑V) catalyzes β1‑6 branching in asparagine‑linked oligosaccharides and is one of the most important glycosyltransferases involved in carcinogenesis, cancer metastasis and immunity. To investigate the biological functions of GnT‑V, the present study developed GnT‑V transgenic (Tg) mice and the role of GnT‑V in e...

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem around the world. Among NAFLD patients, those with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and hepatocellular carcinoma (HCC). To distinguish NASH from simple steatosis and...

Peyer's patches (PPs) play a major role in mucosal immunity. However, their roles in nonsteroidal anti-inflammatory drug-induced enteropathy are poorly understood. Wild-type (WT) and PP-null mice were injected with indomethacin. Twenty-four hours later, the cellular profiles and cytokine levels in the PPs, mesenteric lymph nodes (MLNs), and lamina...

Background Fetuin-A (α2HS-glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)-β1 signaling inhibitor. Serum fetuin-A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin-A as a predictive fibrosis biomarker in NAFLD pat...

Abrogating tolerance is a critical step in the pathogenesis of Crohn's disease (CD). T cell-anergy is one of the main mechanisms of tolerance and is regulated by the gene related to anergy in lymphocytes (GRAIL). This study investigated the expressions and regulation of GRAIL in CD and murine colitis models. Expressions of GRAIL mRNA and protein in...

Purpose: Mac-2 binding protein (Mac-2 bp) is one of the major fucosylated glycoproteins, which we identified with glycol-proteomic analyses. We previously reported that fucosylated glycoproteins are secreted into bile, but scarcely secreted into sera in normal liver and hypothesized that the fucosylation-based sorting machinery would be disrupted...

(Background and Aim) Oligosaccharides are one of the most important factors in the posttranslational modification of proteins and lipids. Glycomics, the systematic study of glycans and glycan-binding proteins in various biological systems, is an emerging field in the post-genomics and post-proteomics era. In particular, fucosylation is one of the m...

Conclusion: Measurement of serum Fuc-Hpt levels can distinguish NASH from non-NASH patients, and predict the presence of ballooning hepatocytes in NAFLD patients with sufficient accuracy. These results support the potential usefulness of measuring Fuc-Hpt levels in clinical practice.

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Histological Characteristics of the biopsy-proven NAFLD patients. (DOCX)

Correlation coefficients of relationships between serum Fuc-Hpt levels and various parameters in the biopsy-proven NAFLD patients. (DOCX)

Various Fuc-Hpt cutoff values for the detection of NASH, the presence of ballooning hepatocyte, and advanced fibrosis. (DOCX)

Multiple logistic regression analysis of factors associated with F3 (diagnosed by FIB-4 index). (DOCX)

Distribution of parameters according to Matteoni’s classification in the biopsy-proven NAFLD patients. (DOCX)

Background: Fucosylated haptoglobin (Fuc-Hpt) is a novel cancer biomarker in a variety of pathological conditions. We previously found that the level of Fuc-Hpt is increased in the sera of patients with pancreatic cancer, and established a lectin antibody ELISA using Aleuria aurantia lectin, which specifically binds to fucosylated residues on olig...

Background: Easily measured and clinically useful biomarkers for inflammatory bowel disease (IBD) are required to advance patient care. We previously reported that the agalactosyl fraction among fucosylated IgG oligosaccharides is increased in IBD, especially Crohn's disease (CD). The present study aimed to establish a simple detection system for...

Background: Oligosaccharide structures and their alterations have important roles in modulating intestinal inflammation. N-Acetylglucosaminyltransferase V (GnT-V) is involved in the biosynthesis of N-acetylglucosamine (GlcNAc) by β1,6-branching on N-glycans and is induced in various pathologic processes, such as inflammation and regeneration. GnT-V...

Oligosaccharide modifications induce various functional changes in immune cells. The galactose-deficient fraction of fucosylated IgG oligosaccharides is increased, whereas that of β-1,4-galactosyltransferase I (B4GalTI) is reduced, in patients with Crohn's disease. We investigated the role of oligosaccharide modification in the pathophysiology of c...