FGF9 modulates Schwann cell myelination in developing nerves and induces a pro-inflammatory environment during injury

J Cell Biochem. 2018 Nov;119(10):8643-8658. doi: 10.1002/jcb.27105. Epub 2018 Jun 28.

Abstract

Myelin sheath is critical for the proper functioning of the peripheral nervous system (PNS), which allows the effective conduction of nerve impulses. Fibroblast growth factor 9 (FGF9) is an autocrine and paracrine protein in the fibroblast growth factor family that regulates cell differentiation and proliferation. Fgf9 Schwann cell (SC) conditional knockout mice were developed to detect the role of FGF9 in the PNS. In our study, the absence of Fgf9 led to delayed myelination in early development. The expression of mature SC-related genes decreased, and the expression of genes associated with immature SCs increased in the Fgf9 knockout mice. These data were consistent with the morphology and praxeology we observed during the development of the peripheral nerves. Extracellular-regulated kinases 1/2 (ERK1/2) are key signals for myelination, and our results showed that Fgf9 ablation led to the inactivation of ERK1/2. Further research was performed to detect the role of FGF9 in peripheral nerve injury. In superoxide dismutase 1-G93A mice with Fgf9 SC knockout, we found that Fgf9 ablation inhibited the expressions of Cd68, Il-1β, and Cd86, which contributed to the degeneration of the axon and myelin sheath.

Keywords: Schwann cell; extracellular-regulated kinases 1/2; fibroblast growth factor 9; inflammation; injury; myelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Apoptosis / physiology
  • Axons / metabolism
  • B7-2 Antigen / metabolism
  • Behavior, Animal / physiology
  • Fibroblast Growth Factor 9 / genetics
  • Fibroblast Growth Factor 9 / metabolism*
  • Gene Knockout Techniques
  • Inflammation / metabolism*
  • Interleukin-1beta / metabolism
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Myelin Sheath / metabolism
  • Neurogenesis / physiology*
  • Peripheral Nerve Injuries / metabolism*
  • Peripheral Nervous System / metabolism
  • Schwann Cells / metabolism*
  • Sciatic Nerve / growth & development
  • Statistics, Nonparametric
  • Superoxide Dismutase / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-2 Antigen
  • CD68 protein, mouse
  • Cd86 protein, mouse
  • Fgf9 protein, mouse
  • Fibroblast Growth Factor 9
  • IL1B protein, mouse
  • Interleukin-1beta
  • SOD1 G93A protein
  • Superoxide Dismutase