Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.

E-GEOD-44562 - Fibroblast growth factor 9 inhibits remyelination via an off target effect on astrocytes in multiple sclerosis

Status
Released on 17 February 2016, last updated on 20 February 2016
Organism
Rattus norvegicus
Samples (8)
Array (1)
Protocols (7)
Description
Failure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination. We identify multiple downstream events induced by FGF9 associated with this effect including increased expression of leukaemia inhibitory growth factor (LIF) and FGF2, both of which are shown to inhibit myelination if present in excess. These studies identify FGF9-dependent signal transduction in astrocytes as a novel target for therapeutic strategies designed to enhance remyelination by endogenous OPC in MS. Gene expression profiles of rat myelinating cultures grown in the presence or absence of FGF9 (100 ng/ml) for 24h and 10 days were generated using Affymetrix GeneChip® Rat Gene 1.0 ST Arrays. Each time point (T1: 24 hrs, and T2: 10 days) has Control (CTR) and Treatment (FGF) groups, with two replicates in each group. In total, 8 arrays were generated from the four groups (CTR-T1, CTR-T2, FGF-T1 and FGF-T2).
Experiment type
transcription profiling by array 
Contacts
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-44562.idf.txt
Sample and data relationshipE-GEOD-44562.sdrf.txt
Raw data (1)E-GEOD-44562.raw.1.zip
Processed data (1)E-GEOD-44562.processed.1.zip
Array designA-GEOD-6247.adf.txt
Links