Biology subjects

Ueki, K.

Publications and source records attributed to Ueki, K..

3 recordsLinked to original sources

bioRxiv2022

Extensive gut virome variation and its associations with host and environmental factors in a population-level cohort

Indigenous bacteriophage communities (virome) in the human gut have a huge impact on the gut bacterial communities (bacteriome), but virome variation at a population scale is not fully investigated yet. Here, we analyse the gut virome in a population-level cohort of 4,198 deeply phenotyped individuals. We discovered thousands of high-quality phage genomes including previously uncharacterized ones with different bacterial hosts than known major phage clades. The distribution of host bacteria was a strong determinant for the distribution of phages, and virome diversity was highly correlated with anti-viral defence mechanisms of the bacteriome, such as CRISPR-Cas and restriction-modification systems. We identified 97 various intrinsic/extrinsic factors that significantly affect the virome, including age, sex, lifestyle, and diet, most of which showed consistent associations with both phages and their predicted bacterial hosts. Among the metadata categories, disease and medication had the strongest effects on the virome structure. Overall, these results present a basis to understand the symbiotic communities of bacteria and their viruses in the human gut, which will facilitate the medical and industrial applications of indigenous viruses.

microbiology↗

bioRxiv2019

Addiction of mesenchymal phenotypes on the FGF/FGFR axis in oral squamous cell carcinoma cells

The epithelial-mesenchymal transition (EMT) is a crucial morphological event that occurs during epithelial tumor progression. ZEB1/2 are EMT transcription factors that are positively correlated with EMT phenotypes and breast cancer aggressiveness. ZEB1/2 regulate the alternative splicing and hence isoform switching of fibroblast growth factor receptors (FGFRs) by repressing the epithelial splicing regulatory proteins, ESRP1 and ESRP2. Here, we show that the mesenchymal-like phenotypes of oral squamous cell carcinoma (OSCC) cells are dependent on autocrine FGF-FGFR signaling. Mesenchymal-like OSCC cells express low levels of ESRP1/2 and high levels of ZEB1/2, resulting in constitutive expression of the IIIc-isoform of FGFR, FGFR(IIIc). By contrast, epithelial-like OSCC cells showed opposite expression profiles for these proteins and constitutive expression of the IIIb-isoform of FGFR2, FGFR2(IIIb). Importantly, ERK was constitutively phosphorylated through FGFR1(IIIc), which was activated by factors secreted autonomously by mesenchymal-like OSCC cells and involved in sustained high-level expression of ZEB1. Antagonizing FGFR1 with either an inhibitor or siRNAs considerably repressed ZEB1 expression and restored epithelial-like traits. Therefore, autocrine FGF-FGFR(IIIc) signaling appears to be responsible for sustaining ZEB1/2 at high levels and the EMT phenotype in OSCC cells.

cancer biology↗

bioRxiv2018

A transgenic mutant mouse line accompanied by the complete deletion of interleukin-33 showed insulin and leptin resistances

Interleukin (IL) -33 has been identified as a member of the IL-1 family. Members of the IL-1 family have been reported to be involved in the regulation of energy homeostasis and glucose metabolism. Homozygous transgenic mutant mice of FLP14 line, that we previously generated, unexpectedly developed mature-onset obesity and diabetes. Through genetic investigations, we found that insertion of the transgenes had resulted in complete deletion of the Il33 gene. These obese male homozygous mutant mice exhibited hyperphagia with hyperleptinemia and insulin resistance caused by increased hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. As a result of examining preobese male homozygous mutant mice to investigate with the exclusion of the effect of obesity, hyperphagia with hyperleptinemina and insulin resistance caused by decreased glucose uptake in skeletal muscle were already observed, but the increased hepatic glucose production was not. To investigate whether the insulin resistance was caused by deletion of the Il33 gene, we treated these preobese homozygous mutant mice with recombinant IL-33 protein and noted a significant improvement in insulin resistance. Thus, insulin resistance in these homozygous mutant mice was caused, at least in part, by IL-33 deficiency, suggesting a favorable role of IL-33 for glucose metabolism in the skeletal muscle.

molecular biology↗