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Transcriptome profiling of vascular fragments in mice intracerebroventricular (ICV) injected with platelet derived dermal growth factor CC (PDGF-CC)

ABSTRACT: Transcriptome profiling of vascular fragments in mice intracerebroventricular (ICV) injected with platelet derived dermal growth factor CC (PDGF-CC)

PROVIDER: PRJNA735549 | ENA |

REPOSITORIES: ENA

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Project description:Platelet-derived growth factor-CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report here a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase (GSK)3beta activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-OHDA-induced Parkinson's dopaminergic neuronal death and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody or shRNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3beta phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival, and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC/receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. PDGF-C deficient mice were bred onto C57BL/6 background for more than six generations and littermates were used. After optic nerve crush (ONC), PDGF-CC protein Ã 1 Âµl of active recombinant human PDGF-CC protein 0.5 Âµg/Âµl (rhPDGF-CC) was injected into mouse vitreous once a week for two weeks. Seven days after the ONC injury and PDGF-CC protein treatment, retinae were harvested and total RNA isolated using the TRIzol reagent (Invitrogen) followed by the RNeasy Mini kit (Qiagen) purification according to the manufacturer's instructions. Microarray assay was performed using the Mouse-6 Expression BeadChips containing approximately 24,000 annotated mouse transcripts (Illumina Inc). Three biological repeats were included in the microarray assay. Two tailed Student's t-test was used for statistical analysis of gene expression data. Functional grouping of the differentially expressed genes was performed using several different tools including the WebGestalt (http://bioinfo.vanderbilt.edu/webgestalt) and the Ingenuity Pathways Analysis (https://analysis.ingenuity.com/pa/login/login.jsp). The supplementary file 'GSE19207_non-normalized.txt' contains raw data for Samples GSM476021-GSM476026.

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Transcriptome profiling of vascular fragments in mice intracerebroventricular (ICV) injected with platelet derived dermal growth factor CC (PDGF-CC)

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