Biology subjects

Shiota, M.

Publications and source records attributed to Shiota, M..

6 recordsLinked to original sources

bioRxiv2026

Periodontal pathogen-derived extracellular vesicles promote EGFR-dependent malignant traits in human pancreatic cancer cells

Extracellular vesicles (EVs) produced by periodontopathic bacteria have been implicated in systemic diseases, yet their mechanistic impact on pancreatic cancer (PAC) cell behavior remains poorly defined. Here, we show that EVs derived from Aggregatibacter actinomycetemcomitans (Aa), but not from Porphyromonas gingivalis or Fusobacterium nucleatum, robustly induce epithelial-mesenchymal transition (EMT), migration, and invasion in human PAC cells. These effects require the Aa genotoxin cytolethal distending toxin (Cdt), which is selectively packaged into Aa-derived EVs and efficiently delivered to host cells. EV-associated Cdt induces DNA damage, triggers a senescence-like transcriptional program, increases EGF sensitivity, and activates the EGFR-ERK/Akt signaling axis independently of TGF{beta} signaling, thereby promoting malignant traits in vitro. Notably, these responses occur in human but not murine PAC cells, revealing species-specific susceptibility to bacterial genotoxins. Together, these findings reveal a previously unrecognized cross-kingdom mechanism by which periodontopathic bacterial EVs promote metastatic traits in human pancreatic cancer cells through Cdt-mediated DNA damage and EGFR-ERK/Akt signaling.

microbiology↗

bioRxiv2025

LRBA promotes drug-induced liver injury and MASLD by scaffolding MAPK activation

LPS-responsive beige-like anchor protein (LRBA) regulates vesicular trafficking and receptor recycling, and its deficiency results in immunodeficiency characterized by hypogammaglobulinemia and autoimmune syndrome. However, its role in liver pathophysiology remains unclear. Here, we reveal a previously unrecognized function of LRBA as a critical intracellular scaffold for mitogen-activated protein kinase (MAPK) activation that promotes liver injury. Lrba-/-mice exhibit reduced acetaminophen (APAP)-induced hepatic necrosis through the suppression of JNK activation. In a model of metabolic dysfunction-associated steatotic liver disease (MASLD) induced by a high-fat, high-cholesterol (HFHC) diet, Lrba deficiency reduces hepatic inflammation, fibrosis, and Kupffer cell activation. Mechanistically, LRBA homodimers directly interact with specific mitogen-activated protein kinase kinase kinases (MAP3Ks), including transforming growth factor-{beta}-activated kinase 1 (TAK1) and mixed-lineage kinase 3 (MLK3), to facilitate their activation. LRBA, which is primarily expressed in hepatocytes under physiological conditions, is upregulated in non-parenchymal cells such as Kupffer cells and cholangiocytes in both HFHC diet-fed mice and patients with MASLD and cirrhosis, linking its scaffolding function to pathological inflammation. Thus, LRBA promotes liver disease progression by amplifying inflammatory signaling.

cell biology↗

bioRxiv2025

LM-GlycoRepo Version 1.0: A novel repository system for mouse tissue glycome mapping data

Lectin microarray (LMA) is a high-sensitive profiling method of protein glycosylation. The increasing use of this method in many studies has led to a growing demand for a repository system that meets the FAIR data principles (Findable, Accessible, Interoperable, and Reusable). Herein, we present a novel repository system, "LM-GlycoRepo," for lectin-based multimodal (LM) data, including LMA data, in accordance with the international guideline MIRAGE (Minimum Information Required for a Glycomics Experiment). As a first step in our efforts to provide a general repository for storing various types of LM data, LM-GlycoRepo Version 1.0 is specialized for mouse tissue glycome mapping data obtained using standardized laser microdissection (LMD)-assisted LMA procedures. This system allows users to deposit datasets containing LMD images, LMA data, and high-resolution lectin staining images as LM data. In addition, this repository adopted an "embargo" system that allows users to specify the release date of datasets, allowing compatibility with an article peer review system. Notably, after the release date, the deposited data were visualized using an existing web tool called LM-GlycomeAtlas. LM-GlycoRepo will evolve into a comprehensive tool for lectin-based multimodal data for various biospecimens, including human samples. LM-GlycoRepo is freely available at the GlyCosmos portal (https://lm-glycorepo.glycosmos.org/lm_glycorepo/).

bioinformatics↗

bioRxiv2021

OTUD1 deubiquitylase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways

Deubiquitylating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-{kappa}B activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-{kappa}B pathway by hydrolysing K63-linked ubiquitin chains from NF-{kappa}B signalling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-{kappa}B activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. The N-terminal intrinsically disordered region of OTUD1, which contains an EGTE motif, is indispensable for KEAP1-binding and NF-{kappa}B suppression. OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1-/--mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways.

cell biology↗

bioRxiv2019

cGMP dynamics underlie thermosensation in C. elegans

Animals sense ambient temperature so that they can adjust their behavior to the environment; they avoid noxious heat and coldness and stay within a survivable temperature range. C. elegans can sense temperature, memorize past cultivation temperature and navigate towards preferable temperature, for which a thermosensory neuron, AFD, is essential. AFD responds to temperature increase from the past cultivation temperature by increasing intracellular Ca2+ level. We aimed to reveal how AFD encodes and memorizes the information of temperature. Although cGMP synthesis is crucial for thermosensation by AFD, whether and how cGMP level temporally fluctuates in AFD remained elusive. We therefore monitored cGMP level in AFD and found that cGMP dynamically responded to temperature change in a manner dependent on past cultivation temperature. Given that cGMP dynamics is supposed to be upstream of Ca2+ dynamics, our results suggest that AFDs memory is formed by simpler molecular mechanisms than previously expected from the Ca2+ dynamics. Moreover, we analyzed how guanylyl cyclases and phosphodiesterases, which synthesize and degrade cGMP, respectively, contributed to cGMP and Ca2+ dynamics and thermotaxis behavior.

neuroscience↗

bioRxiv2019

Thick perirenal fat predicts the growth pattern of renal cell carcinoma

ObjectiveTo examine the relationship between the direction of renal cell carcinoma growth and the visceral/perirenal fat volume.\n\nPatients and Methods: We retrospectively reviewed computed tomography scans of 153 patients with stage 1 renal cell carcinoma who underwent radical or partial nephrectomy in our hospital between January 2013 and July 2016. We calculated the visceral/subcutaneous/perirenal fat volumes using SYNAPSE VINCENT(R). Of the 60 patients, the perirenal fat was immunohistochemically stained for leptin, adiponectin, COX-2 and UCP-1, and the association with outward tumor protrusion was evaluated.\n\nResultsOf the 153 cases, 88 had confirmed outward expansion (57.5%), 110 were classed as pT1a (52 and 58 with outer and inner expansion, respectively), 43 were classed as pT1b (36 and 7 with outer and inner expansion, respectively; P<0.0001). Multivariate logistic regression model showed a trend toward significance in pT1b (vs pT1a, [OR] 6.033, 95%CI=2.409-15.108, P=0.0001), perirenal fat percentage >1.0 (vs [≤]1.0, [OR] 2.596, 95%CI=1.205-5.591, P=0.014). as independent predictors for outer protrusion. Immunohistochemical staining was positive for UCP-1 expression in 31 out of 41 outgrowth types (75.6%), and all 19 endogenous types (100%; P=0.003).\n\nConclusionsRenal cell carcinoma with thick perirenal fat correlates with an increased likelihood of developing outward tumor protrusion; therefore, fat distribution may affect the development of renal cell carcinoma.

cancer biology↗