FGF9 induces neurite outgrowth upon ERK signaling in knock-in striatal Huntington's disease cells

Issa Olakunle Yusuf, Hsiu Mei Chen, Pei Hsun Cheng, Chih Yi Chang, Shaw Jenq Tsai, Jih Ing Chuang, Chia Ching Wu, Bu Miin Huang, H. Sunny Sun, Chuan Mu Chen, Shang Hsun Yang

研究成果: Article同行評審

摘要

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 STHdhQ7/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.

原文English
文章編號118952
期刊Life Sciences
267
DOIs
出版狀態Published - 2021 二月 15

All Science Journal Classification (ASJC) codes

  • 生物化學、遺傳與分子生物學 (全部)
  • 藥理學、毒理學和藥劑學 (全部)

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