Biology subjects

Kataoka, H.

Publications and source records attributed to Kataoka, H..

5 recordsLinked to original sources

bioRxiv2026

Compact serum miRNA qPCR model for pancreatic cancer discrimination with independent and clinical validation

BackgroundFor pancreatic cancer, practical blood-based tests for early detection and postoperative surveillance remain elusive. We sought to develop a qPCR-measurable serum microRNA (miRNA) panel that robustly discriminates pancreatic cancer from non-cancer controls and other malignancies. MethodsWe profiled 255 serum miRNAs in batch 1 (n=72) and selected 27 candidates. Candidates were refined in batch 2 (n=552) and cross-batch evaluation was performed with batch 3 (n=391) to derive a miRNA model. Independent validation used batch 4 (n=616). Clinical relevance was assessed in an independent clinical cohort of resection patients with samples obtained preoperatively and at 1 and 12 months postoperatively. ResultsThe miRNA model trained on batches 2 and 3 achieved an area under the curve (AUC) of 0.91 and 0.83 for pancreatic cancer versus non-cancer controls and non-cancer plus other cancers, respectively, when independently validated in batch 4. Stage-wise AUCs in batch 4 were 0.91 (I), 0.94 (II), 0.86 (III) and 0.90 (IV). In the clinical batch, the score decreased postoperatively (preoperative vs month 1; p<0.01) and was higher in recurrence than non-recurrence (p<0.001). ConclusionsThe developed compact miRNA qPCR assay discriminated pancreatic cancer across independent assay batches and showed clinical relevance for postoperative surveillance. Clinical Trial RegistrationNot applicable.

cancer biology↗

bioRxiv2025

Cdc42 regulates apical membrane fusion via the Rab11a-VAMP2 pathway in salivary gland acinar cells

Epithelial acinar cells of the salivary gland establish apical-basal polarity and secretory competence during development, processes that require tightly coordinated membrane trafficking. The Rho-family GTPase Cdc42 is a key regulator of epithelial polarity, but it has rarely been linked to the vesicle-fusion machinery in vivo. Using mice with acinar cell-specific deletion of Cdc42, we found that Cdc42 loss caused the accumulation of small vesicles near the apical surface, where the water channel AQP5 was retained in clusters and lumen formation was defective. Cdc42-deficient glands showed a selective reduction of two vesicle-associated SNAREs, VAMP2 and VAMP4, whereas VAMP8, the t-SNAREs, and an endocytic marker were unchanged. The corresponding mRNAs were not decreased, indicating that Cdc42 maintains these v-SNAREs through post-transcriptional mechanisms. Cdc42-deficient acinar cells also accumulated condensing vacuoles, a form of immature secretory granule, indicating impaired granule maturation. We propose that Cdc42 coordinates two distinct membrane-remodeling processes by maintaining these v-SNAREs: VAMP2 supports the fusion of AQP5-containing vesicles with the apical membrane, whereas VAMP4 supports secretory granule maturation. These findings identify the vesicle-fusion machinery as a target of Cdc42-dependent polarity control, with potential implications for secretory gland disorders.

cell biology↗

bioRxiv2025

LINC01503-MP is a Mitochondrial Microprotein That Promotes Cell Proliferation and Oxidative Metabolism.

Long non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification of an evolutionarily young microprotein encoded by LINC01503, expressed across several human tissues. This microprotein, designated as LINC01503-MP, localises to the mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies reveal that LINC01503-MP regulates mitochondrial oxygen consumption rate, linking its activity to enhanced metabolic functions and cell proliferation. Interactome analyses identified multiple mitochondrial metabolism-related proteins as potential interaction partners. Our findings show that LINC01503-MP plays a role in the proliferative phenotype associated with LINC01503 upregulation in CRC, suggesting the functional significance of evolutionarily young, lncRNA-derived microproteins in cancer progression.

molecular biology↗

bioRxiv2020

Effect of belt electrode-skeletal muscle electrical stimulation on immobilization-induced muscle fibrosis

PurposeMacrophage accumulation in response to decreasing myonuclei may be the major mechanism underlying immobilization-induced muscle fibrosis in muscle contracture, an intervention strategy suppressing these lesions is necessary. Therefore, this research investigated the effect of belt electrode-skeletal muscle electrical stimulation (B-SES), a new electrical stimulation device, to the macrophage accumulation via myonuclei decrease in immobilization-induced muscle fibrosis. Materials and Methods18 Wistar male rats were divided into the control group, immobilization group (with plaster cast fixation to immobilize the soleus muscles in a shortened position for 2 weeks), and B-SES group (with muscle contractile exercise through B-SES during the immobilization period). B-SES stimulation was performed at a frequency of 50 Hz and an intensity of 4.7 mA, muscle contractile exercise by B-SES was applied to the lower limb muscles for 20 minutes/session (twice a day) for 2 weeks (6 times/week). The bilateral soleus muscles were used for histological, immunohistochemical, biochemical, and molecular biological analyses. ResultsThe number of myonuclei was significantly higher in the B-SES group than in the immobilization group, and there was no significant difference between the B-SES and control groups. The cross-sectional area of type I and II myofibers in the immobilization and B-SES groups was significantly lower than that in the control group, and the cross-sectional area of type I myofibers in the B-SES group was higher than that in the immobilization group. However, Atrogin-1 and MuRF-1 mRNA expression in the immobilization and B-SES groups was significantly higher than those in the control group. Additionally, the number of macrophages, IL-1{beta}, TGF-{beta}1, and -SMA mRNA expression, and hydroxyproline expression was significantly lower in the control and B-SES groups than those in the immobilization group. ConclusionThis research surmised that muscle contractile exercise through B-SES prevented immobilization-induced muscle fibrosis, and this alteration suppressed the development of muscle contracture.

pathology↗

bioRxiv2019

Proteolytic Cleavage by Matriptase Exacerbating Kidney Injury: a Novel Therapeutic Target

Chronic kidney disease (CKD) is a progressive disease, and podocyte injury is a potential mechanism. We found that Matriptase was activated at podocytes in CKD patients and mice while a Matriptase inhibitor slowed the progression of mouse kidney disease. The mechanism could be accounted for by an imbalance favoring Matriptase over its cognate inhibitor, hepatocyte growth factor activator inhibitor type 1 (HAI-1), as conditional depletion of HAI-1 in podocytes accelerates podocyte injury. Intriguingly, the N-terminal of Podocin (Podocin-N), as a consequence of Matriptase cleavage of Podocin, translocates to nucleoli. These results suggest that aberrant activation of Matriptase would cause podocyte injury, and a targeting Matriptase could be a novel therapeutic strategy for CKD patients. Significant statementChronic kidney disease (CKD) is a progressive disease. If podocytes, which are specialized cells of the kidney glomerulus that wrap around capillaries, are injured, kidney injury is exacerbated. Thus, a therapeutic strategy to addressing CKD would be to block podocyte injury. The present study provides evidence that Matriptase cleaves Podocin, a component of podocyte slit membrane, and the N-terminal of podocin translocates to nucleoli, causing kidney injury. Our findings show that the N-terminal of Podocin plays an efficient role for cell fate in podocytes. In addition, the inhibition of Matriptase would be a potential therapeutic target for CKD.

biochemistry↗