Expression data from PDGF-treated SH-SY5Y cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE7403 | GEO | 2008/03/01
SECONDARY ACCESSION(S): PRJNA97897
REPOSITORIES: GEO
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Project description:We conducted a proof-of-concept experiment to explore the possibility of using gene expression-based high throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. To define ERK/PDGFR activation signature, we performed gene expression profiling using Affymetrix U133A arrays 0.5-4 hours following PDGF stimulation, thereby identifying those genes whose expression is correlated with PDGFR activity. In order to identify the component of the gene expression signature that was attributable to ERK activation by PDGFR (as opposed to other pathways downstream of PDGFR), we also pretreated the cells will the ERK inhibitors U0126 and PD98059, and repeated the gene expression profiling studies. Experiment Overall Design: To define ERK/PDGFR activation signature, SH-SY5Y cells were grown to confluence and starved overnight in serum-free medium in order to silence any sustained effects from growth factor signaling. Prior to induction with 50ng/ml PDGF, cells were treated with pathway inhibitors 74 mM Apigenin or 50 mM U0126, or with DMSO (carrier) for 60 minutes. Total RNA was isolated 30 minutes after PDGF addition. Experiments were performed in duplicate. The RNA was processed and hybridized with Affymetrix U133A GeneChips.
2008-04-06 | E-GEOD-7403 | biostudies-arrayexpress
Project description:Human T98G glioblastoma cells were stimulated with platelet-derived growth factor (PDGF) and analyzed by DNA microarrays, which identified 74 immediate-early gene transcripts. Cells were then treated with inhibitors to identify subsets of genes that are targets of the phosphatidylinositol 3-kinase (PI3K) and MEK/ERK signaling pathways. Four groups of PDGF-induced genes were defined: independent of PI3K and MEK/ERK signaling, dependent on PI3K signaling, dependent on MEK/ERK signaling, and dependent on both pathways. Cells were grown in Minimal Essential Medium (Invitrogen) supplemented with fetal calf serum (10%). For growth factor/inhibitor treatments, cells were incubated in serum-free medium for 72 h, and either left unstimulated, or stimulated for 30 min with human PDGF-BB (50 ng/ml) (Sigma). U0126 (Cell Signaling Technology) and LY294002 (BioMol) were added 60 min prior to PDGF addition. Keywords: other
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Project description:ERK/MAPK pathway is one of the highly activated and a crucial player in gastric cancer proliferation and progression. To delineate the complex transcription program associated with ERK/MAPK pathway, PD98059 a known ERK/MAPK inhibitor was treated in AGS, one of the ERK/MAPK signaling pathway over expressed gastric cancer cell line. The resultant changes in genome-wide mRNA expression pattern between control and PD98059 treated was profiled using Human Gene 1.0 ST arrays.
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Project description:Background: Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods: Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results: In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion: Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.
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Project description:L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined. Rats with unilateral 6-OHDA lesions of the nigrostriatal pathway received daily L-DOPA treatment for three weeks, and abnormal involuntary movements (AIMs) were assessed every other day. PD98059 was injected in the lateral ventricle daily for 12 days starting from day 10 of L-DOPA treatment. Striatal molecular markers of LID were analyzed together with gene regulation using microarray. The administration of PD98059 significantly reduced AIMs. In addition, ERK activation and other associated molecular changes including ΔFosB were reversed in rats treated with the MEK inhibitor. PD98059 induced significant up-regulation of 418 transcripts and down-regulation of 378 transcripts in the striatum. Tyrosine hydroxylase (Th) and aryl hydrocarbon receptor nuclear translocator (Arnt) genes were down-regulated in lesioned animals and up-regulated in L-DOPA-treated animals. Analysis of protein levels showed that PD98059 reduced the striatal TH. These results support the association of p-ERK1/2, ΔFosB, p-H3 to the regulation of TH and ARNT in the mechanisms of LID, and pinpoint other gene regulatory changes, thus providing clues for identifying new targets for LID therapy.
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