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Updated: Apr 18, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination
Hema Mohan1,2, Anita Friese3, Stefanie Albrecht4
1Institute of Clinical Neuroimmunology, Ludwig Maximilian University Munich, Marchioninistraße 15, D-81377, Munich, Germany. hema.mohan@ukmuenster.de.
Abstract:
Chronic demyelination is a pathological hallmark of multiple sclerosis (MS). Only a minority of MS lesions remyelinates completely. Enhancing remyelination is, therefore, a major aim of future MS therapies. Here we took a novel approach to identify factors that may inhibit or support endogenous remyelination in MS. We dissected remyelinated, demyelinated active, and demyelinated inactive white matter MS lesions, and compared transcript levels of myelination and inflammation-related genes using quantitative PCR on customized TaqMan Low Density Arrays. In remyelinated lesions, fibroblast growth factor (FGF) 1 was the most abundant of all analyzed myelination-regulating factors, showed a trend towards higher expression as compared to demyelinated lesions and was significantly higher than in control white matter. Two MS tissue blocks comprised lesions with adjacent de- and remyelinated areas and FGF1 expression was higher in the remyelinated rim compared to the demyelinated lesion core. In functional experiments, FGF1 accelerated developmental myelination in dissociated mixed cultures and promoted remyelination in slice cultures, whereas it decelerated differentiation of purified primary oligodendrocytes, suggesting that promotion of remyelination by FGF1 is based on an indirect mechanism. The analysis of human astrocyte responses to FGF1 by genome wide expression profiling showed that FGF1 induced the expression of the chemokine CXCL8 and leukemia inhibitory factor, two factors implicated in recruitment of oligodendrocytes and promotion of remyelination. Together, this study presents a transcript profiling of remyelinated MS lesions and identified FGF1 as a promoter of remyelination. Modulation of FGF family members might improve myelin repair in MS.
Insights
Fibroblast growth factor (FGF) 1 promotes myelin repair in multiple sclerosis (MS). This study identified FGF1 in remyelinated MS lesions, suggesting it could be a therapeutic target for enhancing myelin regeneration.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Chronic demyelination characterizes multiple sclerosis (MS), a neurodegenerative disease.
- Complete remyelination is rare in MS lesions, highlighting the need for therapies that enhance myelin repair.
- Identifying factors that support endogenous remyelination is crucial for developing new MS treatments.
Purpose of the Study:
- To identify factors that inhibit or support endogenous remyelination in MS lesions.
- To analyze gene expression profiles in remyelinated and demyelinated MS lesions.
- To investigate the role of fibroblast growth factor 1 (FGF1) in promoting remyelination.
Main Methods:
- Quantitative PCR on customized TaqMan Low Density Arrays to compare gene transcript levels in MS lesions.
- Analysis of gene expression in remyelinated, active demyelinated, and inactive demyelinated white matter MS lesions.
- Functional experiments using cell cultures to assess FGF1's effect on myelination and oligodendrocyte differentiation.
- Genome-wide expression profiling of human astrocytes treated with FGF1.
Main Results:
- Fibroblast growth factor 1 (FGF1) was significantly upregulated in remyelinated MS lesions compared to control white matter.
- FGF1 expression was higher in the remyelinated rim versus the demyelinated core in MS lesions with adjacent de- and remyelinated areas.
- FGF1 accelerated developmental myelination and promoted remyelination in slice cultures, but decelerated oligodendrocyte differentiation, suggesting an indirect mechanism.
- FGF1 induced astrocyte expression of CXCL8 and leukemia inhibitory factor, factors known to recruit oligodendrocytes and promote remyelination.
Conclusions:
- This study presents a transcriptomic profile of remyelinated MS lesions.
- Fibroblast growth factor 1 (FGF1) is identified as a promoter of remyelination in MS.
- Modulating FGF family members may offer a therapeutic strategy to improve myelin repair in multiple sclerosis.
