A5087455340- Extracellular vesicles in disease
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Erythrocyte Function and Pathophysiology
- Immune cells in cancer
- Lipid Membrane Structure and Behavior
- Cell death mechanisms and regulation
- SARS-CoV-2 and COVID-19 Research
- Circular RNAs in diseases
- Pancreatic function and diabetes
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Force Microscopy Techniques and Applications
- Viral Infections and Vectors
- Pancreatitis Pathology and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- RNA regulation and disease
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Genetic Syndromes and Imprinting
- Cellular transport and secretion
- Nanopore and Nanochannel Transport Studies
Kanazawa University
2016-2025
Life Science Institute
2018-2025
Osaka University
2003-2018
Kanazawa Medical University
2017-2018
Japan Science and Technology Agency
2010-2018
Kyoto University
2009-2011
Harvard University Press
2010
Harvard University
2010
Bio-oriented Technology Research Advancement Institution
2005
RIKEN Center for Integrative Medical Sciences
2004
Apoptotic cells expose phosphatidylserine and are swiftly engulfed by macrophages. Milk fat globule epidermal growth factor (EGF) 8 (MFG-E8) is a protein that binds to apoptotic recognizing enhances the engulfment of We report tingible body macrophages in germinal centers spleen lymph nodes strongly express MFG-E8. Many lymphocytes were found on MFG-E8-/- macrophages, but they not efficiently engulfed. The mice developed splenomegaly, with formation numerous centers, suffered from...
Extracellular vesicles (EVs) such as exosomes and microvesicles serve messengers of intercellular network, allowing exchange cellular components between cells. EVs carry lipids, proteins, RNAs derived from their producing cells, have potential biomarkers specific to cell types even states. However, conventional methods (such ultracentrifugation or polymeric precipitation) for isolating disadvantages regarding purity feasibility. Here, we developed a novel method EV purification by using Tim4...
Selective elimination of synaptic connections is a common phenomenon which occurs during both developmental and pathological conditions. Glial cells have central role in the pruning synapses by specifically engulfing degenerating neurites inappropriate connections, but its regulatory mechanisms been largely unknown. To identify mediators this process, we established an vitro cell culture assay for synapse elimination. Neuronal differentiation formation PC12 were induced culturing with nerve...
Apoptotic cells are rapidly phagocytosed by professional phagocytes, such as macrophages and dendritic cells. This process prevents the release of potentially noxious or immunogenic intracellular materials from dying cells, is thought to play a critical role for maintenance normal functions in surrounding tissues. Milk fat globule-EGF-factor 8 (MFG-E8), secreted activated immature links apoptotic promotes phagocytosis Here, we report that an MFG-E8 mutant, designated D89E, carrying point...
Adiponectin, an adipocyte-derived circulating protein, accumulates in vasculature, heart, and skeletal muscles through interaction with a unique glycosylphosphatidylinositol-anchored cadherin, T-cadherin. Recent studies have demonstrated that such accumulation is essential for adiponectin-mediated cardiovascular protection. Here, we demonstrate the adiponectin/T-cadherin system enhances exosome biogenesis secretion, leading to decrease of cellular ceramides. Adiponectin accumulated inside...
Apoptotic cells expose phosphatidylserine on their surface as an "eat me" signal, and macrophages respond by engulfing them. Although several molecules that specifically bind have been identified, the molecular mechanism triggers engulfment remains elusive. Here, using a mouse pro-B cell line, Ba/F3, grows in suspension, we reconstituted of apoptotic cells. The parental Ba/F3 did not engulf transformants expressing T immunoglobulin- mucin-domain-containing molecule 4 (Tim4), type I membrane...
// Kyosuke Matsuzaki 1 , Kazutoshi Fujita Kentaro Jingushi 2 Atsunari Kawashima Takeshi Ujike Akira Nagahara Yuko Ueda Go Tanigawa 3 Iwao Yoshioka 4 Koji 5 Rikinari Hanayama 6 Motohide Uemura Yasushi Miyagawa Kazutake Tsujikawa Norio Nonomura Department of Urology, Osaka University Graduate School Medicine, Osaka, Japan Laboratory Molecular and Cellular Physiology, Pharmaceutical Science, General Medical Center, Police Hospital, Cancer Proteomics Group, Genome Japanese Foundation for...
Abstract Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show while AXL-low expressing EGFR mutated lung cancer ( mut-LC) cells are more sensitive osimertinib than AXL-high mut-LC cells, a small population emerge tolerance. The mediated by increased expression and phosphorylation of insulin-like factor-1 receptor (IGF-1R), caused...
Abstract Methods that enable specific and sensitive quantification of small extracellular vesicles (sEVs) using flow cytometry are still under development. Aggregation or adsorption antibodies causes sub-nano sized particles non-specific binding largely affects the results cytometric analysis single sEVs. Comparison control IgG target-specific is inappropriate because they have different characters. Here, we evaluate four preparation methods for cytometry, including ultracentrifugation,...
Because endogenous extracellular vesicles are involved in important physiological functions, various techniques have been developed for their isolation and evaluation. However, methods evaluating within cells limited. This study presents a technique the direct extraction evaluation of intraluminal (ILVs). combines scanning ion conductance microscopy, electrochemical syringes, confocal microscopy to extract specific structures living cell, achieving high spatial resolution accuracy at...
Small extracellular vesicles (sEVs), which carry lipids, proteins and RNAs from their parent cells, serve as biomarkers for specific cell types biological states. These vesicles, including exosomes microvesicles, facilitate intercellular communication by transferring cellular components between cells. Current methods, such ultracentrifugation Tim-4 affinity method, yield high-purity sEVs. However, despite small size, purified sEVs remain heterogeneous due to varied intracellular origins. In...
The efficient engulfment of apoptotic cells by professional or nonprofessional phagocytes is critical to maintain mammalian homeostasis. To identify molecules involved in the cells, we established a retrovirus-based expression cloning system coupled with assay. By screening cDNA library mouse macrophage cell line, identified two small GTPase family members (RhoG and Rab5) that enhanced cells. examining other members, found Rac1 whereas RhoA inhibited process. Accordingly, dominant-negative...
Abstract A major function of macrophages is to engulf apoptotic cells prevent them from releasing noxious materials as they die. Milk fat globule-EGF-factor 8 (MFG-E8) a glycoprotein secreted by activated that works bridge between and phagocytes specifically recognizing phosphatidylserine exposed on cells. In this study, we found developmental endothelial locus-1 (Del-1), originally identified an embryonic cell protein binds αvβ3 integrin, structurally functionally homologous MFG-E8. That...
During the involution of mammary glands, epithelial cells undergo apoptosis and are cleared for next cycle lactation. The clearance apoptotic is mediated by neighboring macrophages that migrate into glands. Here, we report milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein binds to recognizing phosphatidylserine, was expressed in glands involved engulfment cells. A deficiency MFG-E8 caused accumulation large number globules (MFGs) ducts during involution, indicating excess MFGs...
The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected rare cells peripheral lymphoid organs, but identity these poorly understood. Here, we report that protein-expressing lymph nodes exhibit typical group 3 innate (ILC3) characteristics such as morphology, absence "classical" hematopoietic lineage markers, and dependence on RORγt. Aire+ are more frequent...
3D-AFM showed the presence of distinct nanodomains bulging out from membrane surface, which can be attributed to membrane-associated proteins.
Abstract SARS‐CoV‐2 spike protein (S) binds to human angiotensin‐converting enzyme 2 (hACE2), allowing virus dock on cell membrane follow by viral entry. Here, we use high‐speed atomic force microscopy (HS‐AFM) for real‐time visualization of S, and its interaction with hACE2 small extracellular vesicles (sEVs). Results show conformational heterogeneity flexibility S stalk receptor‐binding domain (RBD), pH/temperature‐induced change S. in an S‐ACE2 complex appears as all‐RBD up conformation....
Abstract Milk fat globule epidermal growth factor 8 (MFG‐E8) is a protein that stimulates the engulfment of apoptotic cells by phagocytes. Here, we show mouse immature dendritic (DC) generated in vitro culturing bone marrow progenitors presence granulocyte‐macrophage colony‐stimulating (GM‐CSF), and Langerhans present skins, expressed MFG‐E8. Bone marrow‐derived macrophages M‐CSF did not express MFG‐E8 DC was found to be secreted as exosomes. The expression significantly suppressed when were...
Small extracellular vesicles (sEVs) play a crucial role in local and distant cell communication. The intrinsic properties of sEVs make them compatible biomaterials for drug delivery, vaccines, theranostic nanoparticles. Although sEV proteomics have been robustly studied, direct instantaneous assessment structure dynamics remains difficult. Here, we use the high-speed atomic force microscopy (HS-AFM) to evaluate nanotopological changes with respect different physicochemical stresses including...
Abstract Apoptotic cells are swiftly phagocytosed by macrophages and immature dendritic cells. In this study, we found that one mouse macrophage cell line (BAM3) engulfed apoptotic thymocytes, but not a lymphoma (WR19L). mAbs inhibited the phagocytosis of thymocytes BAM3 were identified. Purification Ag revealed it was Src homology 2 domain-bearing protein tyrosine phosphatase substrate-1 (SHPS-1). CD47, ligand for SHPS-1, expressed in WR19L. When WR19L transformed with transformants, after...