Distinctive Patterns of PDGF-A, FGF-2, IGF-I, and TGF-β1 Gene Expression during Remyelination of Experimentally-Induced Spinal Cord Demyelination

Hinks, G.L.; Franklin, Robin J.M.

doi:10.1006/mcne.1999.0771

Cited by 211 publications

(165 citation statements)

References 75 publications

Supporting

Mentioning

153

Contrasting

Order By: Relevance

“…We found upregulation of Pdgfa, Pdgfb, Vegfa, Vegfb, Tgfb1, Igf1, and Spp1, all of which have been reported to promote oligodendrocyte differentiation (Baumann and Pham-Dinh, 2001;Bradl and Lassmann, 2010;Chesik et al, 2008;Diemel et al, 2003;Frost et al, 2003;Hinks and Franklin, 1999;Hsieh et al, 2004;Kim et al, 2009;Selvaraju et al, 2004;Vela et al, 2002;Woodruff et al, 2004). Interestingly, we did not find upregulation of Gdnf or Fgf2, as reported by Gudi et al (2011).…”

Section: Discussionsupporting

confidence: 63%

Identification of a microglia phenotype supportive of remyelination

Olah

Amor

Brouwer

et al. 2011

Glia

319

270

View full text Add to dashboard Cite

In multiple sclerosis, endogenous oligodendrocyte precursor cells (OPCs) attempt to remyelinate areas of myelin damage. During disease progression, however, these attempts fail. It has been suggested that modulating the inflammatory environment of the lesion might provide a promising therapeutic approach to promote endogenous remyelination. Microglia are known to play a central role in neuroinflammatory processes. To investigate the microglia phenotype that supports remyelination, we performed genome-wide gene expression analysis of microglia from the corpus callosum during demyelination and remyelination in the mouse cuprizone model, in which remyelination spontaneously occurs after an episode of toxin-induced primary demyelination. We provide evidence for the existence of a microglia phenotype that supports remyelination already at the onset of demyelination and persists throughout the remyelination process. Our data show that microglia are involved in the phagocytosis of myelin debris and apoptotic cells during demyelination. Furthermore, they express a cytokine and chemokine repertoire enabling them to activate and recruit endogenous OPCs to the lesion site and deliver trophic support during remyelination. This study not only provides a detailed transcriptomic analysis of the remyelinationsupportive microglia phenotype but also reinforces the notion that the primary function of microglia is the maintenance of tissue homeostasis and the support of regeneration already at the earliest stages in the development of demyelinating lesions. V

show abstract

Section: Discussionsupporting

confidence: 63%

Identification of a microglia phenotype supportive of remyelination

Olah

Amor

Brouwer

et al. 2011

Glia

319

270

View full text Add to dashboard Cite

show abstract

“…In demyelinating lesions such as in multiple sclerosis, high levels of FGF-2 are produced by reactive astrocytes and macrophages (GomezPinilla et al, 1992;Hinks and Franklin, 1999;Messersmith et al, 2000;Holley et al, 2003). Concomitantly, FGFR1, which is normally low or undetectable in adult white matter (Asai et al, 1993), begins to be expressed by glial cells in lesions (Logan et al, 1992).…”

Section: Fgf-2 and Ol/myelin Pathologymentioning

confidence: 99%

Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage

Fortin¹,

Rom²,

Sun³

et al. 2005

J. Neurosci.

144

166

View full text Add to dashboard Cite

Fibroblast growth factors (FGFs) have been implicated in numerous cellular processes, including proliferation, migration, differentiation, and survival. Whereas FGF-2, the prototypic ligand in a family of 22 members, activates all four tyrosine kinase FGF receptors (FGFR1-FGFR4), other members demonstrate a higher degree of selectivity. Oligodendrocytes (OLs), the myelin-producing cells of the CNS, are highly influenced by FGF-2 at all stages of their development. However, how other FGFs and their cognate receptors orchestrate the development of OLs is essentially undefined. Using a combination of specific FGF ligands and receptor blocking antibodies, we now show that FGF-8 and FGF-17 target OL progenitors, inhibiting their terminal differentiation via the activation of FGFR3, whereas FGF-9 specifically targets differentiated OLs, triggering increases in process growth via FGFR2 signaling; FGF-18 targets both OL progenitors and OLs via activation of both FGFR2 and FGFR3. These events are highly correlated with changes in FGF receptor expression from FGFR3 to FGFR2 as OL progenitors differentiate into mature OLs. In addition, we demonstrate that, although activation of FGFR1 by FGF-2 leads to proliferation of OL progenitors, it produces deleterious effects on differentiated OLs (i.e., aberrant reentry into cell cycle and downregulation of myelin proteins with a loss of myelin membrane). These data suggest that ligand availability, coupled with changes in FGF receptor expression, yield a changing repertoire of ligand-receptor signaling complexes that contribute critically to the regulation of both normal OL development and potential OL/myelin pathogenesis.

show abstract

“…From in vitro OP analyses, PDGF has been predicted to act independently and/or cooperatively with FGF2 as a mitogen for OP cells from the adult rodent and human CNS [23][24][25]. In areas of experimental demyelination, PDGF-A ligand expression is locally upregulated in reactive astrocytes, and proliferating OP cells express PDGF-α receptor (PDGF-αR) [22,26]. Furthermore, PDG-FαR expression is associated with proliferating cells in MS lesions [27].…”

Section: Stimulating Proliferation To Counter Op Depletion In Chronicmentioning

confidence: 99%

“…Areas of acute and chronic demyelination have increased expression of FGF2 ligand and FGF receptors [11,26,36,37]. In contrast with predictions from in vitro studies, OP proliferation in demyelinated lesions was not impaired in FGF2-null mice, indicating that the potential for FGF2 to act as an OP mitogen may not be a significant role of endogenous FGF2 in vivo during demyelination [37].…”

Section: Stimulating Proliferation To Counter Op Depletion In Chronicmentioning

confidence: 99%

Growth factor regulation of remyelination: behind the growing interest in endogenous cell repair of the CNS

Armstrong

2007

Future Neurol.

View full text Add to dashboard Cite

Remyelination facilitates recovery of saltatory conduction along demyelinated axons and may help prevent axon damage in patients with demyelinating diseases, such as multiple sclerosis. The extent of remyelination in multiple sclerosis lesions varies dramatically, indicating a capacity for repair that is not fulfilled in lesions with poor remyelination. In experimental models of demyelinating disease, remyelination is limited by chronic disease that depletes the oligodendrocyte progenitor (OP) population, inhibits OP differentiation into remyelinating oligodendrocytes and/or perturbs cell survival in the lesion environment. Manipulating the activity of growth factor signaling pathways significantly improves the ability of endogenous OP cells to accomplish extensive remyelination. Specifically, growth factors have been identified that can regulate OP proliferation, differentiation and survival in demyelinated lesions. Therefore, growth factors may be key signals for strategies to improve conditions with poor remyelination. Keywords cuprizone; demyelinating disease; FGF; multiple sclerosis; myelin; oligodendrocyte; PDGF; progenitors; remyelination Transition to in vivo analysis during remyelinationAnalysis of growth factors to promote repair in demyelinating diseases has undergone an important transition to in vivo studies and in doing so has revealed much more than the expected results. Characterization of the bipotential oligodendrocyte-type 2 astrocyte or oligodendrocyte progenitor (OP) cell, and the regulation of cell fate by serum components [1] opened the door for in vitro analysis of growth factor responses in the oligodendrocyte lineage. Numerous subsequent in vitro studies identified specific growth factors capable of regulating differentiation, proliferation, migration and survival at specific stages within this lineage. In vitro studies continue to offer distinct advantages for isolating molecular and cellular mechanisms of action and for characterizing the potential of defined growth factors to induce a specific cellular response. In this context, several cytokines and chemokines have been identified as having direct effects on oligodendrocyte lineage cells that are similar to growth factor actions and so they will be discussed together under the rubric of growth factors. This review will focus on recent in vivo remyelination studies designed to test potential growth factor responses identified in vitro. These in vivo studies demonstrate important effects of growth factors in the context of demyelinating disease models in rodents. However, not all growth factor analyses have resulted in the predicted responses. Importantly, several studies have demonstrated a remarkable capacity of endogenous cells to repair the adult CNS, even following chronic demyelination, using modulation of growth factor signaling to better support oligodendrocyte replacement and myelin formation.

show abstract

Distinctive Patterns of PDGF-A, FGF-2, IGF-I, and TGF-β1 Gene Expression during Remyelination of Experimentally-Induced Spinal Cord Demyelination

Cited by 211 publications

References 75 publications

Identification of a microglia phenotype supportive of remyelination

Identification of a microglia phenotype supportive of remyelination

Distinct Fibroblast Growth Factor (FGF)/FGF Receptor Signaling Pairs Initiate Diverse Cellular Responses in the Oligodendrocyte Lineage

Growth factor regulation of remyelination: behind the growing interest in endogenous cell repair of the CNS

Contact Info

Product

Resources

About