|
| Status |
Public on Feb 17, 2016 |
| Title |
Fibroblast growth factor 9 inhibits remyelination via an off target effect on astrocytes in multiple sclerosis |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
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.
|
| |
|
| Overall design |
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).
|
| |
|
| Contributor(s) |
Linington C |
| Citation(s) |
25907862 |
| Submission date |
Feb 21, 2013 |
| Last update date |
May 18, 2016 |
| Contact name |
Manikhandan A V Mudaliar |
| E-mail(s) |
innovatebio@gmail.com
|
| Organization name |
University of Glasgow
|
| Department |
College of Medical, Veterinary and Life Sciences
|
| Lab |
Institute of Infection, Immunity and Inflammation
|
| Street address |
Room B528, Sir Graeme Davies Building, 120 University Place
|
| City |
Glasgow |
| State/province |
Scotland |
| ZIP/Postal code |
G12 8TA |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL6247 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (8)
|
| GSM1086975 |
Rat_myelinating_cultures_untreated_10days_CTR_T2_rep2 |
| GSM1086976 |
Rat_myelinating_cultures_treated_with_FGF9_10days_FGF_T2_rep2 |
| GSM1086977 |
Rat_myelinating_cultures_untreated_24hr_CTR_T1_rep1 |
| GSM1086978 |
Rat_myelinating_cultures_treated_with_FGF9_24hr_FGF_T1_rep1 |
| GSM1086979 |
Rat_myelinating_cultures_untreated_24hr_CTR_T1_rep2 |
| GSM1086980 |
Rat_myelinating_cultures_untreated_10days_CTR_T2_rep1 |
| GSM1086981 |
Rat_myelinating_cultures_treated_with_FGF9_24hr_FGF_T1_rep2 |
| GSM1086982 |
Rat_myelinating_cultures_treated_with_FGF9_10days_FGF_T2_rep1 |
|
| Relations |
| BioProject |
PRJNA190060 |
Less...
More...