PUBLICATION

Fibulin 5, a human Wharton's jelly-derived mesenchymal stem cells-secreted paracrine factor, attenuates peripheral nervous system myelination defects through the Integrin-RAC1 signaling axis

Authors
Won, S.Y., Kwon, S., Jeong, H.S., Chung, K.W., Choi, B.O., Chang, J.W., Lee, J.E.
ID
ZDB-PUB-201028-6
Date
2020
Source
Stem cells (Dayton, Ohio)   38(12): 1578-93 (Journal)
Registered Authors
Jeong, Hui Su, Lee, Ji Eun, Won, So Yeon
Keywords
Charcot-Marie-Tooth disease, Fibulin 5, Schwann cell myelination, actin remodeling, mesenchymal stem cell
MeSH Terms
none
PubMed
33107705 Full text @ Stem Cells
Abstract
In the peripheral nervous system (PNS), proper development of Schwann cells (SCs) contributing to axonal myelination is critical for neuronal function. Impairments of SCs or neuronal axons give rise to several myelin-related disorders, including dysmyelinating and demyelinating diseases. Pathological mechanisms, however, have been understood at the elementary level and targeted therapeutics has remained undeveloped. Here, we identify Fibulin 5 (FBLN5), an extracellular matrix (ECM) protein, as a key paracrine factor of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) to control the development of SCs. We show that co-culture with WJ-MSCs or treatment of recombinant FBLN5 promotes the proliferation of SCs through ERK activation, whereas FBLN5-depleted WJ-MSCs do not. We further reveal that during myelination of SCs, FBLN5 binds to Integrin and modulates actin remodeling, such as the formation of lamellipodia and filopodia, through RAC1 activity. Finally, we show that FBLN5 effectively restores the myelination defects of SCs in the zebrafish model of Charcot-Marie-Tooth (CMT) type 1, a representative demyelinating disease. Overall, our data propose human WJ-MSCs or FBLN5 protein as a potential treatment for myelin-related diseases, including CMT.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
EGFPnkuasgfp1aTg; ue101TgcontrolDay 5IFL
EGFPnkuasgfp1aTg; ue101TgcontrolDay 5IFL
EGFPnkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5IFL
EGFPnkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5IFL
1 - 4 of 4
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Phenotype
Fish Conditions Stage Phenotype Figure
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 4
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5
nkuasgfp1aTg; ue101Tg + MO1-fbln5controlDay 5
1 - 6 of 6
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nkuasgfp1aTgTransgenic Insertion
    ue101TgTransgenic Insertion
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      fbln5MO1-fbln5MRPHLNO
      1 - 1 of 1
      Show
      Fish
      Fish
      nkuasgfp1aTg; ue101Tg
      nkuasgfp1aTg; ue101Tg + MO1-fbln5
      1 - 2 of 2
      Show
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-fbln5polyclonal
        		IgGRabbit
        Ab7-sox10monoclonal
          		IgG1Mouse
          1 - 2 of 2
          Show
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GAL4EFGGAL4
          1 - 2 of 2
          Show
          Mapping
          No data available
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          Citation
          Won, S.Y., Kwon, S., Jeong, H.S., Chung, K.W., Choi, B.O., Chang, J.W., Lee, J.E. (2020) Fibulin 5, a human Wharton's jelly-derived mesenchymal stem cells-secreted paracrine factor, attenuates peripheral nervous system myelination defects through the Integrin-RAC1 signaling axis. Stem cells (Dayton, Ohio). 38(12):1578-93.