Biology subjects

Mizoguchi, T.

Publications and source records attributed to Mizoguchi, T..

4 recordsLinked to original sources

bioRxiv2024

ANGPTL3 regulates the peroxisomal translocation of SmarcAL1 in response to cell growth states

AbstractAngiopoietin-like 3 (ANGPTL3) is a key regulator of lipoprotein metabolism, known for its potent inhibition on intravascular lipoprotein and endothelial lipase activities. Recent studies have shed light on the cellular functions of ANGPTL3. However, the precise mechanism underlying its regulation of cellular lipid metabolism remains elusive. We recently reported that ANGPTL3 interacts with the chromatin regulator SMARCAL1, which plays a pivotal role in maintaining cellular lipid homeostasis. Here, through a combination of in vitro and in vivo functional analyses, we provide evidence that ANGPTL3 indeed influences cellular lipid metabolism. Increased expression of Angptl3 prompted the formation of lipid droplets (LDs) in response to slow growth conditions. Notably, under the conditions, Angptl3 accumulated within cytoplasmic peroxisomes, where it interacts with SmarcAL1, which translocated from nucleus as observed previously. This translocation induced changes in gene expression favoring triglyceride (TG) accumulation. Indeed, ANGPTL3 gene knockout (KO) in human cells increased the expression of key lipid genes, which could be linked to elevated nuclear localization of SMARCAL1, whereas the expression of these genes decreased in SMARCAL1 KO cells. Consistent with these findings, the injection of Angptl3 protein to mice led to hepatic fat accumulation derived from circulating blood, a phenotype likely indicative of its long-term effect on blood TG, linked to SmarcAL1 activities. Thus, our results suggest that the Angptl3-SmarcAL1 pathway may confer the capacity for TG storage in cells in response to varying growth states, which may have broad implications for this pathway in regulating energy storage and trafficking.

cell biology↗

bioRxiv2019

EDEM3 modulates plasma triglyceride level through its regulation of LRP1 expression

Human genetics studies have uncovered genetic variants that can be used to guide biological research and prioritize molecular targets for therapeutic intervention for complex diseases and metabolic conditions. We have identified a missense variant (P746S) in EDEM3 associated with lower blood triglyceride (TG) levels in >300,000 individuals. Functional analyses in cell and mouse models show that EDEM3 deficiency strongly increased the uptake of very low-density lipoprotein and thereby reduced the plasma TG level, as a result of up-regulated expression of LRP1 receptor. We demonstrate that EDEM3 deletion up-regulated the pathways for RNA and ER protein processing and transport, and consequently increased the cell surface mannose-containing glycoproteins, including LRP1. Metabolomics analyses reveal a cellular TG accumulation under EDEM3 deficiency, a profile consistent with individuals with carrying EDEM3 P746S. Our study identifies EDEM3 as a regulator of blood TG, and targeted inhibition of EDEM3 may provide a complementary approach for lowering elevated blood TG concentrations.

genetics↗

bioRxiv2018

Morphofunctional analysis of antigen uptake mechanisms following sublingual immunotherapy with beads in mice

BackgroundRecently, sublingual immunotherapy (SLIT) has been used as a safe and efficient method for the treatment of and immunization against asthma and various allergies. However, the routes of antigen uptake through the mucosa of the oral cavity remain incompletely understood, as do the roles of sex and age in the process. For this purpose, to elucidate the mechanism and efficacy of SLIT among different sexes and ages microbeads were dripped into the sublingual region to mimic antigen uptake by the sublingual mucosa.\n\nMethodsTwenty microliters of either phosphate buffered saline (PBS) or fluorescently labelled microbeads (latex and silica beads) were placed under the tongue of both male and female C57BL/6 mice at young (3 months) and old (6 months) ages. The lower jaw was examined 30 min after administration, and beads were detected with a fluorescence stereomicroscope. Morphological observations of the mucosa of the fluorescent areas were made with scanning electron microscopy (SEM) and an all-in-one light fluorescence microscope (LM). Fluorescence intensity was compared between both sexes and ages.\n\nResultsStereomicroscopic observation revealed fluorescent illuminations in three compartments of the sublingual mucosa: the sublingual caruncles (SC), the oral rostral mucosa (OR) and the buccal mucosa (BM). Interestingly, the fluorescence intensity tended to be higher among females than among males in the SC region in particular. However, there were no significant age-related differences. SEM and LM revealed beads in the lumina of both mandibular ducts and sublingual ducts (Sd). Additionally, the apical cytoplasm of some Sd cells contained silica beads. However, there were no specification in the OR mucosa or BM.\n\nConclusionsThis study reveals the major role Sd play in local immunity via the antigen uptake mechanisms. Furthermore, our data suggest that the efficacy of SLIT in humans could be affected by sex.

immunology↗

bioRxiv2018

Antibacterial effects of nanoimprinted moth-eye film in practical settings

Recent studies report that surfaces displaying micrometer-or nanometer-sized undulating structures exhibit antibacterial effects. In previous work, we described the use of an advanced nanofabrication technique to generate an artificial biomimetic moth-eye film by coating a polyethylene terephthalate (PET) film with nanoscale moth-eye protrusions made from a hydrophilic resin. This moth-eye film exhibited enhanced antibacterial effects in in vitro experiments. The aim of the present study was to verify the antibacterial efficacy of the Moth-eye film in practical environments. Three types of films (Moth-eye film, Flat film, and PET film) were used to compare antibacterial effects. Sample films were pasted onto hand-wash sinks at the testing locations. After several hours of elapsed time, bacteria from the surface of sample films were collected using one of three kinds of culture media stampers (to permit identification of bacterial species). The stampers were incubated for 48 hours at 35 {degrees}C, and the numbers of colonies were counted.\n\nThe number of common bacteria including E. coli and S. aureus from the Moth-eye film was significantly lower than that from the PET film (p<0.05) and that from the Flat film at 1 hour (p<0.05). This study found that the Moth-eye film had durability of antibacterial effect and the Moth-eye structure (PET coated with nanoscale cone-shaped pillars) had a physical antibacterial effect from the earlier time points. Therefore, the Moth-eye film might be useful for general-purpose applications in practical environments.

microbiology↗