Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination

Hema Mohan; Anita Friese; Stefanie Albrecht; Markus Krumbholz; Christina L Elliott; Ariel Arthur; Ramesh Menon; Cinthia Farina; Andreas Junker; Christine Stadelmann; Susan C Barnett; I. Huitinga; Hartmut Wekerle; Reinhard Hohlfeld; Hans Lassmann; Tanja Kuhlmann; Chris Linington; Edgar Meinl

doi:10.1186/s40478-014-0168-9

Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination

Hema Mohan, Anita Friese, Stefanie Albrecht, Markus Krumbholz, Christina L Elliott, Ariel Arthur, Ramesh Menon, Cinthia Farina, Andreas Junker, Christine Stadelmann, Susan C Barnett, I. Huitinga, Hartmut Wekerle, Reinhard Hohlfeld, Hans Lassmann, Tanja Kuhlmann, Chris Linington, Edgar Meinl

Netherlands Institute for Neuroscience (NIN)

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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.

Original language	English
Pages (from-to)	178
Journal	Acta neuropathologica communications
Volume	2
Issue number	1
DOIs	https://doi.org/10.1186/s40478-014-0168-9
Publication status	Published - 11 Dec 2014

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Mohan, H., Friese, A., Albrecht, S., Krumbholz, M., Elliott, C. L., Arthur, A., Menon, R., Farina, C., Junker, A., Stadelmann, C., Barnett, S. C., Huitinga, I., Wekerle, H., Hohlfeld, R., Lassmann, H., Kuhlmann, T., Linington, C., & Meinl, E. (2014). Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination. Acta neuropathologica communications, 2(1), 178. https://doi.org/10.1186/s40478-014-0168-9

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title = "Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination",

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.",

author = "Hema Mohan and Anita Friese and Stefanie Albrecht and Markus Krumbholz and Elliott, {Christina L} and Ariel Arthur and Ramesh Menon and Cinthia Farina and Andreas Junker and Christine Stadelmann and Barnett, {Susan C} and I. Huitinga and Hartmut Wekerle and Reinhard Hohlfeld and Hans Lassmann and Tanja Kuhlmann and Chris Linington and Edgar Meinl",

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Mohan, H, Friese, A, Albrecht, S, Krumbholz, M, Elliott, CL, Arthur, A, Menon, R, Farina, C, Junker, A, Stadelmann, C, Barnett, SC, Huitinga, I, Wekerle, H, Hohlfeld, R, Lassmann, H, Kuhlmann, T, Linington, C & Meinl, E 2014, 'Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination', Acta neuropathologica communications, vol. 2, no. 1, pp. 178. https://doi.org/10.1186/s40478-014-0168-9

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T1 - Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination

AU - Mohan, Hema

AU - Friese, Anita

AU - Albrecht, Stefanie

AU - Krumbholz, Markus

AU - Elliott, Christina L

AU - Arthur, Ariel

AU - Menon, Ramesh

AU - Farina, Cinthia

AU - Junker, Andreas

AU - Stadelmann, Christine

AU - Barnett, Susan C

AU - Huitinga, I.

AU - Wekerle, Hartmut

AU - Hohlfeld, Reinhard

AU - Lassmann, Hans

AU - Kuhlmann, Tanja

AU - Linington, Chris

AU - Meinl, Edgar

PY - 2014/12/11

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N2 - 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.

AB - 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.

U2 - 10.1186/s40478-014-0168-9

DO - 10.1186/s40478-014-0168-9

M3 - Article

C2 - 25589163

SN - 2051-5960

VL - 2

SP - 178

JO - Acta neuropathologica communications

JF - Acta neuropathologica communications

IS - 1

ER -

Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination

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