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FGF21 impedes peripheral myelin development by stimulating p38 MAPK/c-Jun axis.

Yunzhong Zhang1,2, Ketao Jiang1, Guoqing Xie1

  • 1Key Laboratory for Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregenetation, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong, Jiangsu, China.

Journal of Cellular Physiology
|July 14, 2020
PubMed
Summary

Fibroblast growth factor 21 (FGF21) inhibits peripheral nervous system myelination. FGF21 negatively regulates Schwann cell myelination via the p38 MAPK/c-Jun pathway.

Keywords:
Schwann cellsc-Junfibroblast growth factor 21p38 MAPKperipheral myelination

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Cell Biology

Background:

  • Fibroblast growth factor 21 (FGF21) is a metabolic hormone primarily from the liver.
  • FGF21 promotes central nervous system remyelination.
  • Its role in peripheral nervous system (PNS) myelination is unexplored.

Purpose of the Study:

  • Investigate the role of FGF21 in PNS myelination.
  • Determine the molecular mechanisms underlying FGF21's action on Schwann cells.

Main Methods:

  • Analyzed Fgf21 expression in relation to myelin genes.
  • Treated primary Schwann cells (SCs) with recombinant FGF21.
  • Injected FGF21 or anti-FGF21 antibody into neonatal rats.
  • Assessed myelination markers and MAPK signaling pathways (ERK, p38).

Main Results:

  • FGF21 expression inversely correlated with myelin gene expression in the PNS.
  • FGF21 treatment reduced myelination gene expression in SCs.
  • FGF21 injection inhibited sciatic nerve myelination; anti-FGF21 antibody accelerated it.
  • FGF21 activated ERK and p38 MAPK pathways in SCs and sciatic nerves.
  • The p38 MAPK/c-Jun pathway, not ERK, mediated FGF21's inhibitory effect.

Conclusions:

  • FGF21 acts as a negative regulator of PNS myelin development.
  • This regulation occurs through the activation of the p38 MAPK/c-Jun signaling axis in Schwann cells.