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Project description:Human granulosa cells (GCs), obtained during medical reproductive procedures can be cultured and are a cellular model for the human ovary. Oxygen concentrations are regarded as important regulators of GCs. We examined consequences of low (1%) O2 versus standard atmospheric conditions in cultured human GCs for four days. A proteomic analysis of three pools of human GCs was performed. While differences between the pools of GCs were noted, the abundance of 133 proteins was significantly increased in hypoxia in all samples, whereas the abundance of 391 proteins was decreased.
2023-12-20 | PXD042934 | Pride
Project description:Stress elicits inflammatory and autoimmune diseases while concurrently triggering the production of glucocorticoids (GCs), renowned for their anti-inflammatory effects. In addition, IL-17-producing helper T (Th17) cells are pivotal in initiating inflammation and certain autoimmune disorders. However, whether stress-induced GCs exacerbate inflammatory and autoimmune diseases through Th17 cells remains elusive. Here, we show that GCs facilitate the differentiation and survival of Th17 cells in mice. GCs inhibit the expression of TCF1, a negative regulator of Th17 cell differentiation, thereby increasing pathogenic TCF1low Th17 cells characterized by high glycolytic activity. Remarkably, mice lacking the glucocorticoid receptor (GR), specifically in T cells, manifest less severe experimental autoimmune encephalomyelitis (EAE) and inflammatory colitis. Moreover, stress-induced GCs augment the population of Th17 cells, intensify their IL-17 production, and provoke neutrophil recruitment, resulting in severe inflammation and substantial weight loss in the colitis model. This study demonstrates that stress-induced GCs exacerbate inflammation and autoimmunity by fostering Th17 cell differentiation.
2025-07-31 | GSE235250 | GEO
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases due to their potent immune suppressive properties.
2019-03-03 | GSE109438 | GEO
Project description:Glucocorticoids (GCs) are essential steroid hormones that regulate the immune system. GCs have been widely used to treat various inflammation disorders and auto-immune diseases, due to their potent immune repression properties.
2019-03-03 | GSE117057 | GEO
Project description:Previous studies suggested a role of acetylcholine (ACh) in the regulation of the ovary. A target receptor, alpha 7 nicotinic ACh receptor (CHRNA7; encoded by CHRNA7), is expressed in the human ovary, e.g. by stromal cells, oocytes and human granulosa cells (GCs). The objective of this study was to explore its functions in cultured, in vitro fertilization (IVF)-derived GCs. For this, GCs exposed to 1% O2 were treated with the selective CHRNA7-agonist PNU 282987 for 24 h.
2025-09-02 | PXD059511 | Pride
Project description:Glucocorticoids (GCs) have a long history of use as therapeutic agents for numerous skin diseases. Surprisingly, their specific molecular effects are largely unknown. To characterize GC action in epidermis, we compared the transcriptional profiles of primary human keratinocytes untreated and treated with dexamethasone (DEX) for 1, 4, 24, 48 and 72 hours using large-scale microarray analyses. The majority of genes were found regulated only after 24 hours and remained regulated throughout the treatment. In addition to expected anti-inflammatory genes, we found that GCs regulate cell fate, tissue remodeling, cell motility, differentiation and metabolism. GCs not only effectively block signaling by TNF-alpha and IL-1 but also by IFN-gamma, which was not previously known. Specifically, GCs suppress the expression of essentially all IFN-gamma-regulated genes, including IFN-gamma receptor and STAT-1. GCs also block STAT-1 activation and nuclear translocation. Unexpectedly, GCs have anti-apoptotic effects in keratinocytes by inducing the expression of anti-apoptotic and repressing pro-apoptotic genes. Consequently, GCs treatment blocked UV-induced apoptosis of keratinocytes. GCs have a profound effect on wound healing by inhibiting cell motility and the expression of pro-angiogenic factor VEGF. They play an important role in tissue remodeling and scar formation by suppressing the expression of TGF-beta-1 and -2, MMP1, 2, 9 and 10 and inducing TIMP-2. Finally, GCs promote terminal stages of epidermal differentiation while simultaneously inhibiting the early stages. These results provide new insights into the beneficial and adverse effects of GCs in epidermis, defining the participating genes and mechanisms that coordinate the cellular responses important for GC-based therapies. Human epidermal keratinocytes are grown in delipidized, phenolphtalein-free medium and left as controls or treated with 0.1μM dexamethasone. Time course of treated and parallel control samples over a 72 hr period was performed twice with independent batches of cells.
2011-01-07 | E-GEOD-26487 | biostudies-arrayexpress
Project description:A four-dimensional data-independent acquisition(4D-DIA) approach was used to analyse protein expression in glucocorticoid-sensitive (GCS) and glucocorticoid-resistant (GCR) children with ITP. 47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group.
2023-11-28 | PXD046260 | Pride
Project description:Gastric cancers (GCs) are often diagnosed in advanced stages, owing to non-specific clinical symptoms at early stages that resemble Acid Peptic Diseases (APDs). Despite recent efforts, a simple, liquid biopsy-based, multi-protein panel pre-diagnostic assay that can differentiate GCs from APDs is lacking. Parallelly, Mass Spectrometry (MS)-based targeted proteomics methods including Multiple Reaction Monitoring (MRM) are being progressively utilised as method-of-choice to build Laboratory Developed Tests (LDTs). An MS-MRM LDT that can quantify a panel of serum proteins was developed and tested in 135 serum samples from treatment-naïve cases of GCs, APDs, and healthy individuals.
2025-09-18 | PXD064371 | Pride
Project description:Human primary granulosa cells (GCs) derived from women, undergoing oocyte retrieval, can be cultured and are a cellular model for the study of human ovarian functions. In vitro they change rapidly, resembling initially cells of the preovulatory follicle and then cells of the corpus luteum. They are derived from individual patients and their different medical history, lifestyle and age lead to heterogeneity. Thus, cells can rarely be ideally matched for cellular experiments or, if available, only in small quantities. We reasoned that cryopreservation of human GCs may be helpful. Previous studies indicated feasibility of such an approach, but low survival of GCs was reported and consequences on GC functionality were only partially evaluated. We tested a slow freezing protocol (employing FCS and DMSO) of GCs upon isolation from follicular fluid. We compared cryopreserved and subsequently thawed cells with fresh, not cryopreserved ones, from the same patients. About 80 % of human GCs survived freezing/thawing. Neither morphology, nor levels of cell-cell contact, mitochondrial and steroidogenic genes were different between the two groups in cells cultured for 1-5 days. A proteomic analysis revealed no statistical significance in the abundance of a total of 5962 proteins. Both groups produced comparable basal levels of progesterone and responded similarly to hCG with elevation of progesterone. Taken together, we describe a rapid and readily available method for the cryopreservation of human GCs. We anticipate that it will allow future large-scale experiments and may thereby improve cellular studies with human ovarian cells.
2021-07-28 | PXD025632 | Pride
Project description:Advanced maternal age (AMA) patients experience decreased success from assisted reproductive technologies (ART), attributed to quantity and quality of oocytes, which is significantly influenced by the health of surrounding granulosa cells (GCs). In this study, we compared mRNA and microRNA (miRNA) transcriptomes between young (<32 y.o.) and AMA (>38 y.o.) patients' GCs to identify ovarian aging molecular signatures. Granulosa cells were isolated from 18 patients’ follicular fluid, and RNA was isolated for sequencing and subsequent bioinformatics analysis. We identified 293 and 21 differentially expressed genes (DEGs) and miRNAs (DE miRNA), respectively, between young and AMA GCs (P value < 0.05, FDR < 0.25, Fold Change > 1.5). Highly expressed mitochondrial-encoded genes, MT-ND3, MT-ND6, and MT-CYB are upregulated in young GCs. Pathway analysis indicates DEGs play a role in inflammation, cytokine signaling, extracellular matrix (ECM) remodeling, and angiogenesis. Some key DEGs include CXCL8, IL1B, NLRP3, SIGIRR, ANGPT2, ADAM8, and ADAMTS14. Additionally, target gene prediction and pathway analysis of DE miRNA indicates both up- and downregulated miRNA in young GCs are likely targeting genes associated with cell signaling, mitochondrial function, oxidative stress, apoptosis, and senescence pathways in addition to cytokine signaling, angiogenesis, and ECM remodeling. To further investigate regulatory mechanisms, we looked at the convergence of DEGs with predicted target genes of DE miRNA and identified miR-483-3p, miR-1268a, miR-4497, miR-7704, miR-135a-5p, miR-1261, and miR-4791 as key regulators of pathways involved with inflammation, ECM, and angiogenesis. The gene expression data suggests aged GCs have an impaired ability to elicit the same pro-inflammatory response combined with a dysregulation of angiogenesis and ECM remodeling when compared to young GCs, and miRNA may be playing a key role in the regulation of these key ovulatory events.
2025-03-12 | GSE270749 | GEO