2. Academic Validation
  3. Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease

Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease

  • Cell Physiol Biochem. 2018;48(2):605-617. doi: 10.1159/000491889.
Issa Olakunle Yusuf 1 2 3,  Pei-Hsun Cheng 3,  Hsiu-Mei Chen 3,  Yu-Fan Chang 3,  Chih-Yi Chang 3,  Han-In Yang 3,  Chia-Wei Lin 3,  Shaw-Jenq Tsai 3 4,  Jih-Ing Chuang 3 4,  Chia-Ching Wu 4 5,  Bu-Miin Huang 4 5,  H Sunny Sun 4 6,  Shang-Hsun Yang 1 3 4
Affiliations

Affiliations

  • 1 Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Cheng Kung University and Academia Sinica, Taipei, Taiwan.
  • 2 Institute of Clinical Medicine, Tainan, Taiwan.
  • 3 Department of Physiology, Tainan, Taiwan.
  • 4 Institute of Basic Medical Sciences, Tainan, Taiwan.
  • 5 Department of Cell Biology and Anatomy, Tainan, Taiwan.
  • 6 Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
PMID: 30021209 DOI: 10.1159/000491889
Abstract

Background/aims: Huntington's disease (HD) is a heritable neurodegenerative disorder, and there is no cure for HD to date. A type of Fibroblast Growth Factor (FGF), FGF9, has been reported to play prosurvival roles in Other neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. However, the effects of FGF9 on HD is still unknown. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD.

Methods: In this study, STHdhQ7/Q7 (WT) and STHdhQ111/Q111 (HD) striatal knock-in cell lines were used to evaluate the neuroprotective effects of FGF9. Cell proliferation, cell death and neuroprotective markers were determined via the MTT assay, propidium iodide staining and Western blotting, respectively. The signaling pathways regulated by FGF9 were demonstrated using Western blotting. Additionally, HD transgenic mouse models were used to further confirm the neuroprotective effects of FGF9 via ELISA, Western blotting and immunostaining.

Results: Results show that FGF9 not only enhances cell proliferation, but also alleviates cell death as cells under starvation stress. In addition, FGF9 significantly upregulates glial cell line-derived neurotrophic factor (GDNF) and an anti-apoptotic marker, Bcl-xL, and decreases the expression level of an apoptotic marker, cleaved Caspase 3. Furthermore, FGF9 functions through ERK, Akt and JNK pathways. Especially, ERK pathway plays a critical role to influence the effects of FGF9 toward cell survival and GDNF production.

Conclusions: These results not only show the neuroprotective effects of FGF9, but also clarify the critical mechanisms in HD cells, further providing an insight for the therapeutic potential of FGF9 in HD.

Keywords

Cell signaling; Fibroblast Growth Factor 9; Glial cell line-derived neurotrophic factor; Huntington’s disease; Striatal cell death.

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