Similar Datasets
Project description:Atrial fibrillation (AFib) and the risk of its lethal complications are worsened by atrial fibrosis. A recent study implicates osteopontin (encoded by Spp1) secreted by atrial TREM2+ macrophages in this fibrosis. Here, we show that silencing Spp1 in TREM2+ cardiac macrophages using an antibody-siRNA conjugate (ARC) reduces atrial fibrosis and suppresses AFib, thus offering a new immunotherapy for this common arrhythmia.
2024-09-12 | GSE272503 | GEO
Project description:We conducted a proteomic analysis of secretome and EV samples isolated from the conditioned medium of lung cancer LC (A549, NCI-H23, and NCI-H460) and CRC (Caco2, HCT116, and HT-29) cell line models.
2025-05-07 | PXD057205 | Pride
Project description:Gene expression microarray data of bone marrow derived macrophages using GM-CSF(GM-BMMs) co-cultured with E0771 breast tumor cells
2014-09-08 | E-GEOD-54073 | ExpressionAtlas
Project description:To determine the molecular signaling pathways responsible for USP16 regulation of cell growth, RNA sequencing was conducted on NCI-H23 cells with or without USP16 knockdown
2021-07-20 | GSE160388 | GEO
Project description:Endothelial cells (ECs) not only form passive blood conduits. They actively contribute to nutrient transport and establish an instructive vascular niche to maintain and restore organ homeostasis. The role of the endothelium in the maintenance of muscle glucose homeostasis is however poorly understood. Here we show that, in skeletal muscle, the endothelial glucose transporter 1 (Glut1/Slc2a1) controls glucose uptake not via affecting transendothelial glucose transport, but via vascular niche control of muscle resident macrophages. Lowering endothelial glut1 via genetic depletion (glut1EC) or upon short-term high-fat diet increased angiocrine osteopontin (OPN/SPP1) secretion, promoting resident muscle macrophage activation and proliferation which impairs muscle insulin sensitivity. Consequently, co-deleting Spp1 from the endothelium prevented macrophage accumulation, reduced muscle OPN levels, and improved insulin sensitivity in glut1EC mice. Mechanistically, glut1-dependent endothelial glucose metabolic rewiring increased OPN in a serine metabolism-dependent fashion. Our data illustrate how the glycolytic endothelium creates a niche that controls resident muscle macrophage phenotype and function and directly links resident muscle macrophages to the development of muscle insulin resistance.
2024-07-26 | GSE263417 | GEO
Project description:Endothelial cells (ECs) not only form passive blood conduits. They actively contribute to nutrient transport and establish an instructive vascular niche to maintain and restore organ homeostasis. The role of the endothelium in the maintenance of muscle glucose homeostasis is however poorly understood. Here we show that, in skeletal muscle, the endothelial glucose transporter 1 (Glut1/Slc2a1) controls glucose uptake not via affecting transendothelial glucose transport, but via vascular niche control of muscle resident macrophages. Lowering endothelial glut1 via genetic depletion (glut1EC) or upon short-term high-fat diet increased angiocrine osteopontin (OPN/SPP1) secretion, promoting resident muscle macrophage activation and proliferation which impairs muscle insulin sensitivity. Consequently, co-deleting Spp1 from the endothelium prevented macrophage accumulation, reduced muscle OPN levels, and improved insulin sensitivity in glut1EC mice. Mechanistically, glut1-dependent endothelial glucose metabolic rewiring increased OPN in a serine metabolism-dependent fashion. Our data illustrate how the glycolytic endothelium creates a niche that controls resident muscle macrophage phenotype and function and directly links resident muscle macrophages to the development of muscle insulin resistance.
2024-07-26 | GSE263416 | GEO
Project description:Transcription profiling of mouse bone marrow macrophages (BMM) compared to BMM co-cultured with 4T1.2 breast cancer cells, treated with tumour cell supernatant, or RAW macrophage cell line
2015-11-17 | E-MTAB-4064 | ExpressionAtlas
Project description:Osteopontin depletion in macrophages perturbs proteostasis via regulation of UCHL1-UPS pathway and activation of mitochondria-mediated apoptosis
Osteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow derived macrophages (BMM), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMM upregulates OPN expression, promoting an anti inflammatory, phagocytic, pro-healing phenotype, whereas OPN inhibition triggered a pro-inflammatory phenotype. Here, we applied a global proteome profiling via mass spectrometry analysis to gain a mechanistic understanding of OPN suppression versus induction in macrophages. We identified over 630 differentially expressed proteins (DEPs) in OPN knockout (OPNKO) or GA stimulated versus wild type (WT) macrophages. Two topmost downregulated DEPs in OPN deficient macrophages were ubiquitin C terminal hydrolase L1 (UCHL1), a crucial component of ubiquitin proteasome system (UPS), and the anti inflammatory Heme oxygenase 1 (HMOX 1), whereas GA stimulation upregulated their expression. We further confirmed UCHL1 expression in BMM, and its direct interaction with OPN in protein complex. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome mitochondria-mediated apoptosis (e.g. ROS, Lamp1/2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g. 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome bioinformatics data, Western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages, inducing apoptosis and inhibiting translation, whereas GA stimulated OPN induction restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via regulation of cell viability, UCHL1 UPS pathway, and protein synthesis, indicating its potential application in immune-based therapy.
2023-02-08 | MSV000091221 | MassIVE
Project description:Semophorin (SEMA) 6A showed capability to reduce the SEMA3A-derived supression of T cells. However, the effect of SEMA6A on the other immune cells was still unclear. Therefore, we performed gene expression analysis using an Affymetrix mouse genome 430 2.0 array to investigate the potential immune cells regualted by the interaction of SEMA6A and SEMA3A. Thus, we predicted other possible immune cells regulated by SEMA6A using GSEA to analyze the microarray data of co-cultured splenocytes. The reuslts revealed that SEMA6A decreased the SEMA3A-mediated inhibition of B cells and induced activities of dendritic cells in a SEMA3A-indepenet manner. Moreover, M1 and M2 macrophages were not influenced by SEMA6A and SEMA3A.
2020-04-16 | GSE148718 | GEO
Project description:Osteopontin (OPN, Spp1-/-) is considered detrimental in pulmonary fibrosis. However, effect of OPN produced by AMs during pulmonary fibrosis is not known. We used bulk RNA sequencing to analyze the effect of OPN in AMs from bleomycin treated mice.
2024-03-04 | GSE202348 | GEO