Biology subjects

Ito, G.

Publications and source records attributed to Ito, G..

7 recordsLinked to original sources

bioRxiv2025

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

immunology↗

bioRxiv2025

Fetal reversion from diverse lineages sustains the intestinal stem cell pool and confers stress resilience

Plasticity is a central mechanism underlying the robust regenerative capacity of the intestinal epithelium. Two major plasticity have been described: spatial plasticity, in which differentiated cells revert to crypt base columnar cells (CBCs), and fetal reversion into revival stem cells (revSCs). However, the relationship among these two stem cell populations and differentiated cells remains to be clarified. Here, we demonstrated the bidirectional interconversion between CBCs and revSCs. Using lineage tracing, injury models and villus culture, we show that absorptive enterocytes can reprogram into revSCs and regenerate CBCs. These findings position fetal reversion as an entry point to spatial plasticity, establishing a regenerative hierarchy where CBCs, revSCs, and enterocytes collectively orchestrate intestinal repair. Furthermore, we identified revSCs as a highly stress-tolerant stem cell population, whose emergence is crucial for preserving the stem cell pool. Our results establish fetal reversion as a cellular escape mechanism safeguarding epithelial regeneration under inflammatory conditions.

cell biology↗

bioRxiv2022

Determination of a target image of freshwater fishes composition in a mitigation project using eDNA metabarcoding methods

Establishing realistic targets for fish community composition is needed to assess the effectiveness of river restoration projects. We used environmental DNA (eDNA) metabarcoding with MiFish primers to obtain estimates of fish community composition across 17 sites upstream, downstream and within a restoration mitigation project area (Kaihotsu- Kasumi) located in the Shigenobu River system, Ehime Prefecture, Japan. We evaluate the benefits of using eDNA to quickly, sensitively, and extensively gather data to establish existing fish community composition in the restoration area, as well as potential future short-term, medium-term, and long-term targets of species assemblages that could realistically emerge following dispersal into the project area from upstream and downstream populations. We compare results from eDNA metabarcoding with species lists obtained from contemporaneous capture surveys and historical information. Nonmetric multidimensional scaling plots of community composition obtained from eDNA surveys showed that the Kaihotsu-Kasumi restoration area and surrounding river reaches were divided into three clusters: upper reaches, middle and lower reaches, and estuarine reaches. The Kaihotsu- Kasumi restoration area sites were included in the group containing the middle and lower reaches of the inflow and outflow rivers that were near the restoration area. We detected a total of twenty-six species in this group, twenty-one native species and five non-native species. Therefore, these native species were considered suitable as short-term target species with high potential for dispersal into Kaihotsu-Kasumi restoration area. By comparison, only 14 species would have been selected as target species based on capture surveys and historical literature. One factor increasing the resolution of our eDNA surveys was our ability to identify the presence of intraspecific lineages of Misgurnus anguillicaudatus (Clades A and B), which were missed by the capture surveys. These results indicate that the eDNA metabarcoding method can provide more comprehensive and realistic short-term target species estimates than capture surveys, as well as provide higher resolution monitoring through intraspecific lineage detection.

ecology↗

bioRxiv2022

Adaptation to ER-stress via serine glycine metabolism licences STING signalling and CMV control in intestinal epithelial cells

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract. While the molecular causality between endoplasmic reticulum (ER) stress and intestinal inflammation is widely accepted, the metabolic consequences of chronic ER-stress on the pathophysiology of IBD remain unclear. By using in vitro, ex vivo, in vivo mouse models and patient datasets, we identified a distinct polarisation of the mitochondrial one-carbon (1C) metabolism and a fine-tuning of the amino acid uptake in intestinal epithelial cells tailored to support GSH and NADPH metabolism upon chronic ER-stress. This metabolic phenotype strongly correlates with IBD severity and therapy-response. Mechanistically, we uncover that both chronic ER-stress and serine limitation disrupt cGAS/STING-signalling, impairing the epithelial response against viral and bacterial infection, fuelling experimental enteritis. Consequently, antioxidant treatment restores STING function and virus control. Collectively, our data highlight the importance of the plasticity of serine metabolism to allow proper cGAS/STING-signalling and innate immune responses upon chronic inflammation in the gut.

cell biology↗

bioRxiv2021

BORCS6 is involved in the enlargement of lung lamellar bodies in Lrrk2 knockout mice

Leucine-rich repeat kinase 2 (LRRK2) has been implicated in the pathogenesis of Parkinson disease. It has been shown that Lrrk2 knockout (KO) rodents have enlarged lamellar bodies (LBs) in their alveolar epithelial type II cells, although the underlying mechanisms remain unclear. Here we performed proteomic analyses on LBs isolated from Lrrk2 KO mice and found that the LB proteome is substantially different in Lrrk2 KO mice compared with wild-type mice. In Lrrk2 KO LBs, several Rab proteins were increased, and subunit proteins of BLOC-1-related complex (BORC) were decreased. The amount of surfactant protein C was significantly decreased in the bronchoalveolar lavage fluid obtained from Lrrk2 KO mice, suggesting that LB exocytosis is impaired in Lrrk2 KO mice. We also found that the enlargement of LBs is recapitulated in A549 cells upon KO of LRRK2 or by treating cells with LRRK2 inhibitors. Using this model, we show that KO of BORCS6, a BORC subunit gene, but not other BORC genes, causes LB enlargement. Our findings implicate the LRRK2-BORCS6 pathway in the maintenance of LB morphology.

cell biology↗

bioRxiv2019

Erythropoietic miR-486-5p and miR-451a depletion from whole blood-derived small RNA sequencing libraries

Erythroid-specific miR-451a and miR-486-5p are two of the most dominant microRNAs (miRNAs) in human peripheral blood. In small RNA sequencing libraries, their overabundance reduces diversity as well as complexity and consequently causes negative effects such as missing detectability and inaccurate quantification of low abundant miRNAs. Here we present a simple, cost-effective and easy to implement hybridization-based method to deplete these two erythropoietic miRNAs from blood-derived RNA samples. By utilization of blocking oligonucleotides, this method provides a highly efficient and specific depletion of miR-486-5p and miR-451a, which leads to a considerable increase of measured expression as well as detectability of low abundant miRNA species. The blocking oligos are compatible with common 5 ligation-dependent small RNA library preparation protocols, including commercially available kits, such as Illumina TruSeq and Perkin Elmer NEXTflex. Furthermore, the here described method and oligo design principle can be easily adapted to target many other miRNA molecules, depending on context and research question.

molecular biology↗

bioRxiv2019

Knowledge of Chagas disease in Latin American migrant population living in Japan and factors associated with knowledge level

BackgroundChagas disease (CD), typically confined to the Latin America (LA) region, is emerging as a global health problem. In Japan, as in the rest of world, the under-diagnose rate of CD is alarmingly high. Various studies have highlighted the importance of informed knowledge in the seeking behavior. Educational integrative activities, with consideration for socio-cultural factors, can help increase the knowledge of the participants. There has been no studies that analyze the difference in knowledge, before and after these educational activities. This study aimed to qualitatively and quantitatively investigate the knowledge, behavior and attitude toward CD among LA migrants in Japan and to evaluate the effectiveness of the community educational activity in increasing knowledge of CD.\n\nMethodologyThis cross-sectional study involved two questionnaires to analyze the knowledge of the LA migrant participants before and after the community activity (CA) in four cities in Japan (Oizumi, Suzuka, Hadano, and Nagoya).\n\nPrincipal FindingsA total of 75 participants were enrolled, predominantly Bolivians from hyperendemic areas. The baseline knowledge of CD was low. However, most of them were familiar with the disease although less than 10% of them had been tested for CD before. Living in Japan for more than 10 years and previously being tested for CD were the factors associated with better knowledge. The conducted CA significantly improved the knowledge of the participants. They associated the term \"Chagas\" mostly with fear and concern. In contrast to other studies, the level of stigmatization was low. The barriers in care seeking behavior were language, migration process and difficulties to access to the healthcare system.\n\nConclusionEducational activities with integrative approach are useful to increase knowledge of CD. The activity brings the possibility to explore not only the level of knowledge, but also to reveal the experience and to understand the needs of the people at risk.\n\nAuthor SummaryThough the incident rate of Chagas disease (CD) has fallen, more than 7 million people are affected worldwide. The CD prevalence is under-estimated because just 1% of these affected people can access to the diagnosis and treatment. This situation is maintaining mainly for the lack of implication of socio-cultural factors in the interventions to decrease the burden of the disease. Educational activities with integral approach are useful to increase the knowledge of the people at risk. People that have being tested for CD before or living in Japan for more than 10 years have better knowledge about the disease, suggesting the importance of knowledge in the seeking behavior. The authors recommend the implementation of educational activities with integral approach as a strategy to improves the knowledge of Chagas disease among Latin America migrants in Japan.

scientific communication and education↗