1. FGF9 induces neurite outgrowth upon ERK signaling in knock-in striatal Huntington's disease cells.
- Author
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Yusuf IO, Chen HM, Cheng PH, Chang CY, Tsai SJ, Chuang JI, Wu CC, Huang BM, Sun HS, Chen CM, and Yang SH
- Subjects
- Animals, Butadienes pharmacology, Cell Line, Cells, Cultured, Corpus Striatum metabolism, Enzyme Inhibitors pharmacology, Fibroblast Growth Factor 9 antagonists & inhibitors, Humans, Huntingtin Protein genetics, Huntingtin Protein metabolism, Huntington Disease metabolism, Mice, Mice, Transgenic, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Neurites drug effects, Neuronal Outgrowth physiology, Nitriles pharmacology, Nuclear Proteins metabolism, Oxidative Stress drug effects, Recombinant Proteins pharmacology, Signal Transduction, Sulfones pharmacology, Fibroblast Growth Factor 9 metabolism, Fibroblast Growth Factor 9 pharmacology, MAP Kinase Signaling System drug effects, Neurites metabolism
- Abstract
Aims: Huntington's disease (HD) is a neurodegenerative disease that causes deficits in neurite outgrowth, which suggests that enhancement of neurite outgrowth is a potential direction by which to improve HD. Our previous publications showed that fibroblast growth factor 9 (FGF9) provides anti-apoptosis and anti-oxidative functions in striatal cell models of HD through the extracellular signal-regulated kinases (ERK) pathway, and FGF9 also stimulates cytoskeletons to enhance neurite outgrowth via nuclear factor kappa B (NF-kB) signaling. In this study, we further demonstrate the importance of the ERK pathway for the neurite outgrowth induced by FGF9 in HD striatal models., Materials and Methods: FGF9 was treated with ERK (U0126) or NF-kB (BAY11-7082) inhibitors in STHdh
Q7/Q7 and STHdhQ111/Q111 striatal knock-in cell lines to examine neurite outgrowth, cytoskeletal markers, and synaptic proteins via immunofluorescence staining and Western blotting. NF-kB activity was analyzed by NF-kB promoter reporter assay., Key Findings: Here, we show that suppression of ERK signaling significantly inhibits FGF9-induced neurite outgrowth, cytoskeletal markers, and synaptic proteins in HD striatal cells. In addition, we also show suppression of ERK signaling significantly decreases FGF9-induced NF-kB activation, whereas suppression of NF-kB does not decrease FGF9-induced ERK signaling. These results suggest that FGF9 activates ERK signaling first, stimulates NF-kB upregulation, and then enhances neurite outgrowth in HD striatal cells., Significance: We elucidate the more detailed mechanisms of neurite outgrowth enhanced by FGF9 in these HD striatal cells. This study may provide insights into targeting neurite outgrowth for HD therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2021
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