FGF9 induces neurite outgrowth upon ERK signaling in knock-in striatal Huntington's disease cells
| Autor: | Jih Ing Chuang, Shaw Jenq Tsai, Issa Olakunle Yusuf, Bu Miin Huang, Chuan-Mu Chen, Shang Hsun Yang, Pei Hsun Cheng, Chih Yi Chang, H. Sunny Sun, Chia Ching Wu, Hsiu Mei Chen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Fibroblast Growth Factor 9 Neurite MAP Kinase Signaling System Neuronal Outgrowth Mice Transgenic Fibroblast growth factor 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Mice 0302 clinical medicine FGF9 Downregulation and upregulation Nitriles Butadienes Neurites Animals Humans Sulfones General Pharmacology Toxicology and Pharmaceutics Enzyme Inhibitors Cytoskeleton Cells Cultured Huntingtin Protein Chemistry Kinase NF-kappa B Nuclear Proteins General Medicine Corpus Striatum Recombinant Proteins Cell biology stomatognathic diseases Oxidative Stress 030104 developmental biology Huntington Disease Cell culture Signal Transduction |
| Zdroj: | Life sciences. 267 |
| ISSN: | 1879-0631 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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