Effect of SPP1 stimulation on gene expression of human skin fibroblast cell line (HSF)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE274625 | GEO | 2026/07/01
REPOSITORIES: GEO
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Project description:Effect of SPP1 stimulation on gene expression of human skin fibroblast cell line (HSF)
| PRJNA1147299 | ENA
Project description:Mutations in the Fbn1 gene cause Marfan Syndrome (MFS) and are associated with excessive transforming growth factor beta (TGF-β) signalling activation, which contributes to extracellular matrix (ECM) homeostasis disruption, thoracic aortic aneurysm (TAA) and dissection development. In this study, we aimed to explore the underlying events contributing to ECM metabolism imbalance and TAA and dissection formation in MFS. We performed sequencing analysis and investigated differentially expressed genes as well as cellular communication using CellChat. Fourteen ECM-related differentially expressed genes (DEGs) were identified. Among the 14 genes, secreted phosphoprotein 1 (Spp1) was involved in multiple pathological processes. We then stimulated primary mouse perivascular fibroblasts and aortic SMCs with recombinant Spp1 and recorded increased collagen expression in fibroblasts and decreased expression of Acta2 and Tagln in SMCs. We also investigated SPP1 levels in healthy controls and patients with TAA and found that elevated SPP1 levels were associated with an increased risk of TAA. Our results have indicated that Spp1 regulates ECM changes in fibroblasts and SMCs contractility during TAA. We believe that our study makes a significant contribution to the literature because our results suggest that Spp1 may serve as a potential target for TAA treatment.
2024-12-12 | GSE190720 | GEO
Project description:Abstract: Cancer-associated fibroblasts (CAFs) play an important role in the induction of chemo-resistance. The objectives of this study were to clarify the mechanism underlying CAF-mediated sorafenib/lenvatinib resistance and identify a novel therapeutic target to overcome resistance to sorafenib/lenvatinib in hepatocellular carcinoma (HCC). Methods: Whole transcriptome sequencing (WTS) data of nine pairs of CAFs and para-cancer-associated fibroblasts (PAFs) were analyzed to identify key molecules that induce resistance to tyrosine kinase inhibitors (TKIs). In vitro and in vivo experiments were performed to validate selected targets and related mechanisms. Plasma secreted phosphoprotein 1 (SPP1) expression levels prior to sorafenib/lenvatinib treatment as well as progression-free survival (PFS) and overall survival (OS) of an advanced HCC cohort (n=42) were evaluated using Kaplan–Meier analysis. Results: Co-culturing CAFs and HCC cells significantly reduced the responsiveness of HCC cells to sorafenib/lenvatinib, in vitro and in vivo. Systematic integrative analysis of the WTS data of CAFs/PAFs and publicly available gene expression data indicated that CAF-derived SPP1 (CAF-SPP1) was suitable for use as a candidate molecule to induce sorafenib/lenvatinib resistance. An evaluation of the mechanisms involved indicated that CAF-SPP1 increased phosphorylation of PKCɑ, which then activated rapidly accelerated fibrosarcoma (RAF)-extracellular signal-related kinase 1/2-signal transducer and activator of transcription 3 (STAT3) and phosophoinositide 3-kinase (PI3K)-AKT-mechanistic target of rapamycin kinase (mTOR) in HCC cells. SPP1 inhibitors reversed CAF-induced sorafenib/lenvatinib resistance in vitro and in vivo. Patients showing high plasma SPP1 prior to sorafenib/lenvatinib treatment exhibited significantly poor PFS (P=0.005) and OS (P=0.041). Conclusions: CAF-SPP1 enhances sorafenib/lenvatinib resistance in HCC by alternatively activating oncogenic pathways via PKCɑ phosphorylation. Inhibition of CAF-SPP1 may be utilized as a therapeutic strategy against TKI resistance in HCC. Plasma SPP1 level prior to TKI treatment shows potential as a promising biomarker for predicting sorafenib/lenvatinib response in advanced HCC patients.
2022-12-24 | GSE192912 | GEO
Project description:Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double strand break (DSB) formation that in budding yeast is directed in gene promoters by histone H3K4 di/trimethylation. This histone modification is indeed recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me and recruits a DSB protein, Mer2, to promote DSB formation close to gene promoters. How Set1C and Mer2 related functions of Spp1 are connected is not clear.
2018-01-30 | PXD007590 | Pride
Project description:SPP1 stimulation of human leukocytes drives proinflammatory monocyte activation and differentiation of dysregulated CD274(PDL-1)pos neutrophil phenotype.
2022-05-02 | E-MTAB-10430 | biostudies-arrayexpress
Project description:We analyzed gene expression in human fibroblasts stimulated by platelet-derived growth factor-BB (PDGF-BB) or basic fibroblast growth factor (bFGF) for 1h and 24h. The results of two independent experiments were merged. SAM analysis identified 116 relevant probe sets. Hierarchical clustering of these probe sets showed divergent early gene regulation by PDGF and FGF but overlapping late response. We first analyzed genes commonly regulated by PDGF-BB and b-FGF more than 2 fold after 24h of stimulation and we found that these two growth factors repressed FOXO. We then focused on the early gene expression response induced by both growth factors. We performed a fold change analysis and found 114 probe sets regulated by PDGF-BB and 42 probe sets regulated by b-FGF, 37 of which were shared between the two gene lists . Keywords: Time course, cell Treatment comparison
2009-03-16 | GSE14256 | GEO
Project description:Rationale: The role of club cells in the pathology of Idiopathic Pulmonary Fibrosis IPF is not well understood. PDIA3, an endoplasmic reticulum (ER) based redox chaperone catalyzes the cysteine disulfide bonds (-S-S-) in various fibrosis-related proteins; however, mechanisms of action of PDIA3 in pulmonary fibrosis is not fully elucidated. Objectives: To examine the role of club cells and PDIA3 in the pathogenesis of pulmonary fibrosis (PF) and therapeutic potential of inhibition of PDIA3 in PF. Methods: The impact of PDIA3 and aberrant club cells in PF was studied by retrospective analysis of human transcriptome data from LGRC, and specific deletion and inhibition of PDIA3 in club cells and blocking Osteopontin (SPP1) downstream of PDIA3 in mice. Measurements and Main Results: The PDIA3 along with club cell secretory protein (SCGB1A1 or CCSP) signatures are upregulated in IPF compared to control patients, and PDIA3 increases correlate with a decrease in lung function in IPF patients. The Bleomycin (BLM) model of PF showed increases in aberrant CCSP and PDIA3 positive cells in the lung parenchyma. Ablation of Pdia3, specifically in CCSP cells, decreases CCSP cells along with PF in mice. The therapeutic administration of a PDI inhibitor LOC14 reversed the BLM-induced CCSP cells and PF in mice. The proteomic screen of the PDIA3 partners revealed SPP1 as a major interactor in PF. Blocking SPP1 attenuated the development of PF in mice. Conclusions: Collectively, this study demonstrates a new relationship of club cells, with PDIA3, SPP1, and a putative pathological function of club cells in pulmonary fibrosis.
2021-11-11 | PXD021715 | Pride
Project description:Marginal zone (IgM[hi] CD23[lo]MZ) and Follicular B (IgM[lo] CD23[hi]FB) cells in SCID Spp1-/- mice have different profile from naïve and Spp1-/- B cells. In addition, OPN mutation on the SCID background induced upregulation of genes involved in DNA replication and class switching of B cells
2021-08-20 | GSE118826 | GEO
Project description:Patients affected by idiopathic pulmonary fibrosis (IPF), a progressive chronic and eventually fatal lung disease with unknown causes, suffer from delayed diagnosis due to the lack of predictive markers for disease development. Prior studies focused on the cellular and transcriptomic changes found in lung tissue during established, often terminal, lung disease. In clinical routine, bronchoscopy is applied for diagnosis and staging of suspected IPF affected individuals, thus providing us with a clinically applicable window, to study the cellular and transcriptional changes within affected individuals. Here we study a patient collective consisting of 11 IPF affected individuals and 11 healthy controls. We investigate their single cell transcriptomic profile alongside their cellular surface phenotype of alveolar-resident immune cells. Single cell transcriptional analysis reveals early accumulation of SPP1+ macrophages (SPP1+M) within the alveolar space as an early cellular sign of IPF, in the absence of a decline in lung function. Early-stage IPF accumulated SPP1+M were characterized by high expression of lipid storage and handling genes, accumulation of intracellular cholesterol and expression of proinflammatory cytokine expression. In silico developmental trajectory analysis revealed that SPP1+M are likely derived from monocytes. Finally to confirm the clinical diagnostic value of SPP1+ M we developed a flow cytometry panel to rapidly identify and test for the presence of SPP1+ M in bronchoalveolar lavage samples and confirm our observation in an independent validation cohort. Taken together, we show that SPP1+ M are associated with early IPF pathogenesis in the absence of an obvious decline in lung function, thus providing a clinically valuable markers for easy diagnosis of early IPF in clinical practice.
2026-02-07 | GSE252465 | GEO
Project description:Embryonic brain macrophages from Wild type or Spp1 KO mice embryo E14.5 and E18.5 were analysed by single cell RNA sequencing
2024-02-27 | E-MTAB-13581 | biostudies-arrayexpress