Biology subjects

Setoyama, D.

Publications and source records attributed to Setoyama, D..

4 recordsLinked to original sources

bioRxiv2026

Multi-Omics Mapping of Human Kidney Reveals Complement-Mediated Cellular Dynamics During Progression of Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a major cause of glucocorticoid-resistant nephrosis, yet its pathogenesis remains unclear. To define the molecular and cellular landscape of FSGS, we employed multi-omics approaches on independent human kidney biopsy cohorts. Proteomics revealed enhanced immune and complement activation. Spatial transcriptomics using a target gene panel constructed from the proteomics highlighted alternative pathway activation driven by complement factor D as a prominent feature. Complement activation emerged in glomeruli alongside altered signaling in podocytes and parietal epithelial cells (PECs): Podocytes displayed reduced PECAM1 and elevated macrophage migration inhibitory factor (MIF) signaling, and PECs display complement and collagen signaling as early events, and progressively acquired cellular activation, prompting glomerular fibrosis. These pathogenic signals propagated into adjacent interstitial regions, paralleling immune cell infiltration and fibrosis. These results uncover dynamics of dysregulated intercellular interactions originated from podocyte and PECs underlying the pathogenesis of FSGS, which provides insights into potential stage-specific interventions.

systems biology↗

bioRxiv2024

MitoNEET reduces the mitochondrial oxidative phosphorylation during epithelial-mesenchymal transition

Mitochondrial functions range from catabolic to anabolic, which are tightly coordinated to meet cellular demands for proliferation and motility. MitoNEET is a mitochondrial outer membrane protein with a CDGSH domain and is involved in mitochondrial function. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose their epithelial characteristics and acquire mesenchymal traits, such as motility, which is a vital step for organism development and wound-healing. Cellular motility is associated with high ATP consumption owing to lamellipodia formation, which is supported by upregulated oxidative phosphorylation (OXPHOS) capacity. However, how mitoNEET is involved in the regulation of OXPHOS capacity and subsequent cellular motility remains unclear. Here we show that loss of mitoNEET regulation during EMT impairs both OXPHOS enhancement and cell motility in non-transformed NMuMG mouse mammary gland epithelial cells. We found that mitoNEET is downregulated during EMT, and that the aberrant expression of mitoNEET abolishes the upregulation of OXPHOS, leading to the inhibition of cell motility. Furthermore, we found that mitoNEET topology may be crucial for the regulation of the mitochondrial electron transfer chain, suggesting an additional regulatory pathway for OXPHOS capacity. Our results demonstrate that mitochondrial OXPHOS capacity during EMT is partly regulated by the dynamics of the outer membrane protein. We believe that our findings are the first step towards understanding the mechanisms by which mitochondrial outer membrane protein topology affects organelle functions.

cell biology↗

bioRxiv2023

Leveraging Machine Learning to Uncover the Hidden Links between Trusting Behavior and Biological Markers

Understanding the decision-making mechanisms underlying trust is essential, particularly for patients with mental disorders who experience difficulties in developing trust. We aimed to explore biomarkers associated with trust-based decision-making by quantitative analysis. However, quantification of decision-making properties is difficult because it cannot be directly observed. Here, we developed a machine learning method based on Bayesian hierarchical model to quantitatively decode the decision-making properties from behavioral data of a trust game. By applying the method to data of patients with MDD and healthy controls, we estimated model parameters regulating trusting decision-making. The estimated model was able to predict behaviors of each participant. Although there is no difference of the estimated parameters between MDD and healthy controls, several biomarkers were associated with the decision-making properties in trusting behavior. Our findings provide valuable insights into the trusting decision-making, offering a basis for developing targeted interventions to improve their social functioning and overall well-being.

bioinformatics↗

bioRxiv2019

Characterization and function of medium and large extracellular vesicles from plasma and urine by surface antigens and Annexin V

Medium/large extracellular vesicles (m/lEVs) are released by most cell types and are involved in multiple basic biological processes. Analysis of m/lEV levels in blood or urine may help unravel pathophysiological findings in many diseases. However, it remains unclear how many naturally-occurring m/lEV subtypes exist as well as how their characteristics and functions differ from one another. Here, we identified m/lEVs pelleted from plasma and urine samples by differential centrifugation and showed by flow cytometry that they typically possessed diameters between 200 nm and 800 nm. Using proteomic profiling, we identified several proteins involved in m/lEV biogenesis including adhesion molecules, peptidases and exocytosis regulatory proteins. In healthy human plasma, we could distinguish m/lEVs derived from platelets, erythrocytes, monocytes/macrophages, T and B cells, and vascular endothelial cells using various surface antigens. m/lEVs derived from erythrocytes and monocytes were Annexin V positive. In urine, 50% of m/lEVs were Annexin V negative but contained various membrane peptidases derived from renal tubular villi. Urinary m/lEVs, but not plasma m/lEVs, showed peptidase activity. The method we have developed to characterize cell-derived m/lEVs suggests the possibility of clinical applications.

molecular biology↗