Biology subjects

Tominaga, N.

Publications and source records attributed to Tominaga, N..

3 recordsLinked to original sources

bioRxiv2026

Regucalcin-containing extracellular vesicles suppress M2 macrophage polarization and attenuate tumor progression in vivo

Regucalcin (RGN) plays diverse roles in cell biology, highlighting its importance in both physiological and pathological conditions. Prostate cancer patients with higher RGN expression exhibited significantly longer disease-free survival. Although RGN is a cell signaling suppressor, the molecular mechanisms underlying tumor suppression by RGN in the tumor microenvironment through cell-cell communication remain unclear. PC3 prostate cancer cell lines stably expressing RGN or a control vector were generated for this study. Extracellular vesicles (EVs) were isolated from these cell lines using differential ultracentrifugation. The murine macrophage cell line J7441 was treated with isolated EVs, and effects on M2 polarization were evaluated using qRT-PCR and western blot analysis. To assess the potential anti-tumor effects of EVs, PC3 parental cells were subcutaneously implanted at two sites per mouse, followed by intratumoral injection of the respective EVs. Tumor volume was monitored. Harvested fresh frozen tumor tissues underwent immunofluorescence staining for CD206, an M2 macrophage marker. RGN was detected in EVs from RGN-expressing cells, and treatment with these RGN-containing EVs was associated with reduced tumor growth and reduced M2 macrophage polarization in vitro and in vivo. Furthermore, recombinant RGN protein reduced the levels of p-AKT1 and p-ERK1/2. Moreover, the suppression of M2 macrophage polarization by RGN-containing EVs was accompanied by decreased p-AKT1 and p-ERK1/2 in vitro. This study describes an EV-associated mechanism that may contribute to the regulation of macrophage polarization and indicates that RGN-containing EVs merit further evaluation as a candidate approach for cancer treatment. Causal validation, such as macrophage depletion or CD206 knockdown, and evaluation in additional models remain to be addressed in future studies.

cancer biology↗

bioRxiv2026

4-Phenylbutyric Acid Activates an NF-κB - Egr-1 Axis to Control Myoblast Proliferation and ECM Gene Expression Profiles

Myoblast proliferation and differentiation are tightly controlled by epigenetic mechanisms, yet how clinically used epigenetic modulators influence myogenic cell fate remains incompletely understood. Here, we demonstrate that the histone deacetylase inhibitor and chemical chaperone 4-phenylbutyric acid (4-PBA) selectively promotes myoblast proliferation without inducing differentiation in C2C12 cells. Mechanistically, 4-PBA increases histone H3 acetylation at lysines 18 and 27 via downregulation of HDAC5, resulting in activation of NF-{kappa}B p65. Chromatin immunoprecipitation identifies early growth response 1 (Egr-1) as a direct transcriptional target of NF-{kappa}B p65. Transcriptomic analyses reveal that Egr-1 regulates extracellular matrix- and myogenesis-associated gene programs, including multiple collagen genes. Consistently, 4-PBA induces a transcriptional signature that significantly overlaps with Egr-1-dependent gene expression. Functional studies further establish that the NF-{kappa}B p65 - Egr-1 axis is required for 4-PBA-mediated transcriptional remodeling in proliferating myoblasts. Together, these findings uncover an epigenetic mechanism by which 4-PBA modulates myoblast proliferation through HDAC5-dependent histone acetylation and NF-{kappa}B p65 - Egr-1 driven transcriptional programs, providing insight into how epigenetic therapeutics influence skeletal muscle cell behavior. HighlightO_LI4-PBA enhances murine myoblast proliferation independently of differentiation induction. C_LIO_LI4-PBA enhances H3K18 and H3K27 acetylation through downregulation of HDAC5. C_LIO_LINF-{kappa}B p65 activates Egr-1 by directly binding to the Egr-1 promoter region. C_LIO_LI4-PBA stimulates the HDAC5 - NF-{kappa}B p65 - Egr-1 axis drives extracellular matrix-related gene profiles. C_LI

molecular biology↗

bioRxiv2025

Age-dependent Dysferlin Accumulation in Macrophages Promotes STAT1 Activation via Calcium Influx, Impairing Myogenesis

DYSF functions as a regulator of Ca{superscript 2} in the skeletal muscle and facilitates muscle repair following injury. It is also highly expressed in monocytes and macrophages and related to inflammation, immune regulation, and the mononuclear phagocyte system. Macrophages are pivotal in driving myogenesis, and specific cytokine-induced macrophage differentiation plays a role in maintaining skeletal muscle during disease and aging. Thus, a comprehensive understanding of the mechanisms by which DYSF operates in macrophages may inform the development of novel treatments for muscle atrophy. In this study, we demonstrated that DYSF expression is associated with monocyte differentiation and increases with age. Our findings indicate that DYSF overexpression induces the generation of M1-type macrophages, which subsequently secrete inflammatory cytokines and promote cell invasion. Furthermore, we observed that DYSF regulates Ca{superscript 2} influx into the cell and activates the STAT1 signaling pathway, whereas DYSF deficiency suppresses these processes. Macrophages overexpressing DYSF are associated with the inhibition of myoblast differentiation during myogenesis in a co-culture system involving macrophages and myoblasts. Therefore, the balance between the STAT1 signaling pathway and Ca{superscript 2}, which are regulated by DYSF abundance, may play a crucial role in myogenesis.

immunology↗