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

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.

MicroRNA‐mediated inflammation and coagulation effects in rats exposed to an inhaled analog of sulfur mustard

“…FGF9 has been reported to play an important role in the injuryassociated proinflammatory environment, albeit in a neuronal model. 36 In the lung, FGF9 may also be involved in response of reparative cells after injury. 37 The role of EGR2, however, is less clear as it has been shown to be a prosurvival factor involved in inflammation and also a downstream target of NF-κB.…”

“…Both Fgf9 and Egr2 were also upregulated upon CEES treatment. FGF9 has been reported to play an important role in the injury‐associated proinflammatory environment, albeit in a neuronal model 36 . In the lung, FGF9 may also be involved in response of reparative cells after injury 37 .…”

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

“…In accordance with our findings, FGF9 has been characterized as a negative regulator for myelination process in oligodendrocytes as evidenced by multibranched premyelinating oligodendrocytes which interact with nerve fibers but fail to form the myelin sheaths (Lindner et al, 2015). In the PNS, however, FGF9 deficiency led to delayed myelination in early development (Deng et al, 2018). It has been shown that FGF2 inhibits the differentiation from oligodendrocyte progenitor into oligodendrocytes or astrocytes (Azim et al, 2012).…”

“…However, on the contrary, another report revealed that FGF2 does not block oligodendrocyte progenitor differentiation (Zhou & Armstrong, 2007). From the studies presented above, FGF9 and FGF2 play opposite functions in the process of myelination in different anatomical compartments (Deng et al, 2018; Lindner et al, 2015). Similarly, the NGF‐regulated axonal signals present opposite effects on the myelination process, facilitating SC myelination in the PNS, but reducing oligodendrocyte myelination in the CNS (Chan et al, 2004).…”

“…Recently, it has been reported that FGF21 derived from peripheral tissues leaks into the CNS after injury and promotes remyelination in a toxin‐induced demyelination model (Kuroda et al, 2017). In the PNS, the absence of FGF9 leads to delayed myelination in early development (Deng et al, 2018). However, whether FGF21 affects myelination in the PNS, and the underlying molecular mechanisms, are still not clear.…”