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Kazuki Yasuda

Publications and source records attributed to Kazuki Yasuda.

11 recordsLinked to original sources
PubMed2026

Genome-wide DNA methylation profiling during metabolic dysfunction-associated steatohepatitis-related hepatocarcinogenesis in patients in Japan and the United States.

This study aimed to compare ethnicity-related differences in DNA methylation profiles during metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocarcinogenesis in patients from Japan and the United States (US). Genome-wide DNA methylation analysis using the Infinium assay was performed in 36, 148 and 36 samples of normal liver tissue (NLT), non-cancerous liver tissue showing MASH, and MASH-related hepatocellular carcinoma (HCC), respectively (220 samples in total), from the Japan and US cohorts. Principal component analysis revealed that MASH had a distinct DNA methylation profile differing from that of NLT, and that the MASH profiles in the two cohorts differed from each other. DNA methylation alterations of cancer-related genes in MASH were inherited by or strengthened in MASH-related HCC itself, resulting in expression alterations. DNA methylation alterations of FGFR2, FUT4, B3GNT5 and MOSC1 in the precancerous MASH stage were shared by the two cohorts, suggesting that such genes are commonly associated with MASH-related hepatocarcinogenesis. On the other hand, it was suggested that DNA methylation alterations of ZNF611 and SAMD10, and those of SHC1, are involved specifically in MASH-related hepatocarcinogenesis in the Japan and the US cohorts, respectively. These findings suggest that DNA methylation alterations, which may reflect race and lifestyle, are associated with MASH-related hepatocarcinogenesis.

Humans↗
PubMed2003

Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif.

We report the cloning and characterization of a human cDNA predicted to encode a novel hydrophobic protein containing four transmembrane domains and a zinc metalloprotease motif, HEXXH, between the third and fourth transmembrane domains, and have named the molecule metalloprotease-related protein-1 (MPRP-1). The MPRP-1 gene was localized to chromosome 1-p32.3 by radiation hybrid mapping, and Northern blot analysis revealed expression in many organs, with strong expression in the heart, skeletal muscle, kidney and liver. Immunohistochemical analyisis showed that MPRP-1 was localized in the endoplasmic reticulum (ER), and not in the Golgi compartment. Fragments of DNA encoding a segment homologous to the HEXXH motif of MPRP-1 are widely found in bacteria, yeast, plants, and animals. These results suggest that the MPRP-1 may have highly conserved functions, such as in intracellular proteolytic processing in the ER.

Amino Acid Sequence↗
PubMed2003

Rat neurological disease creeping is caused by a mutation in the reelin gene.

Reelin (Reln) is an extracellular matrix protein secreted from distinct neuronal populations and controls neural cell positioning during brain development. Alterations of human RELN have been reported in two pedigrees with an autosomal recessive lissencephaly. Although several alleles of the mouse reeler mutation were identified as disruptions of Reln, there is no other animal model with a confirmed mutation in Reln. We recently established the Komeda Zucker creeping (KZC) rat strain with an autosomal recessive mutation creeping (cre), showing a reeler-like phenotype. We also found that creeping was located in the genomic segment on rat chromosome 4 containing Reln and that the expression level of Reln mRNA was markedly reduced in cre/cre homozygous mutant animals. Here we report positional candidate cloning of creeping, and identify a nucleotide insertion mutation in Reln. This mutation leads to a translational frameshift and results in truncation of the predicted protein in the fourth reelin-specific repeat, removing the C-terminal region required for secretion and function of the protein. We conclude that the mutation detected here is causative and is probably a null allele. The KZC rat is the first rat model with a confirmed Reln mutation and would therefore contribute to the understanding of the Reln function.

Animals↗
PubMed2003

Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis.

In primary adipocytes, insulin receptor substrate (IRS)-1 and -3 are expressed in a comparable amount and play distinct roles in insulin signaling. To examine the roles of these IRS in apoptosis inhibition, we evaluated staurosporine-induced apoptosis in Chinese hamster ovary (CHO) cells overexpressing human insulin receptor and IRS-1 or IRS-3. Overexpression of both IRS protected CHO cells from staurosporine-induced apoptosis. Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. Treatment of these cells with a PI 3-kinase inhibitor LY294002 suppressed apoptosis-inhibitory effects of IRS-1 and IRS-3 as well as the phosphorylation of PKB and FKHRL1. These results indicate that both IRS-1 and IRS-3 take part in apoptosis inhibition through the PI 3-kinase/PKB/forkhead cascade.

Animals↗
PubMed2002

A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity.

Rodents fed fish oil showed less obesity with a reduction of triglyceride synthesis in liver, relative to other dietary oils, along with a decrease of mature form of sterol regulatory element binding protein-1 (SREBP-1) and activation of peroxisome proliferator-activated receptor alpha (PPARalpha). Decrease of mature SREBP-1 protein by fish oil feeding was due to either inhibition of SREBP-1 proteolytic cascade or to decrease of its mRNA. To clarify its mechanism and relation to antiobesity effect, mice were fed fish oil in a range from 10 to 60 energy percent (en%). Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPARalpha activation and a decrease of SREBP-1 mRNA. However, compared with 0 en% fish oil feeding, 10 en% fish oil feeding decreased mature SREBP-1 protein by 50% with concomitant decreases of lipogenic genes, while precursor SREBP-1 protein rather increased by 1.3-fold. These data suggest that physiological doses of fish oil feeding effectively decrease expression of liver lipogenic enzymes by inhibiting SREBP-1 proteolytic cascade, while substantial decrease of SREBP-1 expression is observed in its pharmacological doses, and that activation of PPARalpha rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.

Acetyl-CoA Carboxylase↗
PubMed2002

Cblb is a major susceptibility gene for rat type 1 diabetes mellitus.

The autoimmune disease type 1 diabetes mellitus (insulin-dependent diabetes mellitus, IDDM) has a multifactorial etiology. So far, the major histocompatibility complex (MHC) is the only major susceptibility locus that has been identified for this disease and its animal models. The Komeda diabetes-prone (KDP) rat is a spontaneous animal model of human type 1 diabetes in which the major susceptibility locus Iddm/kdp1 accounts, in combination with MHC, for most of the genetic predisposition to diabetes. Here we report the positional cloning of Iddm/kdp1 and identify a nonsense mutation in Cblb, a member of the Cbl/Sli family of ubiquitin-protein ligases. Lymphocytes of the KDP rat infiltrate into pancreatic islets and several tissues including thyroid gland and kidney, indicating autoimmunity. Similar findings in Cblb-deficient mice are caused by enhanced T-cell activation. Transgenic complementation with wildtype Cblb significantly suppresses development of the KDP phenotype. Thus, Cblb functions as a negative regulator of autoimmunity and Cblb is a major susceptibility gene for type 1 diabetes in the rat. Impairment of the Cblb signaling pathway may contribute to human autoimmune diseases, including type 1 diabetes.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2002

Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is due to interactions between cigarette smoke exposure and other risk factors. Genetic variations of human beta-defensin-1 (hBD-1), an endogenous antimicrobial peptide in the airway, were investigated in 60 patients and 213 healthy volunteers by single-strand conformation and restriction fragment length polymorphism analysis and DNA sequencing. Four nucleotide variations in the 5' and 3' untranslated regions and two nonsynonymous substitutions in the coding region were identified. Of these, a newly found Ile38 variant was observed in 15.0% of patients but only in 2.8% of healthy individuals and was significantly associated with the disease (OR = 6.1, 95% confidence intervals 2.0-8.3, P = 0.0012). More than 80% of those with Ile38 experienced sputum production for more than 3 months during the follow-up period. Genetic variations in hBD-1 may define a high-risk subgroup of COPD where the component of chronic bronchitis is predominant.

Aged↗
PubMed2002

Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.

An adipocyte-derived peptide, adiponectin (also known as GBP28), is decreased in subjects with type 2 diabetes. Recent genome-wide scans have mapped a diabetes susceptibility locus to chromosome 3q27, where the adiponectin gene (APM1) is located. Herein, we present evidence of an association between frequent single nucleotide polymorphisms at positions 45 and 276 in the adiponectin gene and type 2 diabetes (P = 0.003 and P = 0.002, respectively). Subjects with the G/G genotype at position 45 or the G/G genotype at position 276 had a significantly increased risk of type 2 diabetes (odds ratio 1.70 [95% CI 1.09-2.65] and 2.16 [1.22-3.95], respectively) compared with those having the T/T genotype at positions 45 and 276, respectively. In addition, the subjects with the G/G genotype at position 276 had a higher insulin resistance index than those with the T/T genotype (1.61 +/- 0.05 vs. 1.19 +/- 0.12, P = 0.001). The G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 +/- 0.85 microg/ml, G/T: 13.7 +/- 0.87 microg/ml, T/T: 16.6 +/- 2.24 microg/ml, P = 0.01) in subjects with higher BMIs. Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes.

Adiponectin↗
PubMed2002

Genome-wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate Loci on 7p and 11p.

The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4alpha [HNF-4alpha]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.

Adult↗
PubMed2002

[MODY genes].

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Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗