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

Issa Olakunle Yusuf, Pei Hsun Cheng, Hsiu Mei Chen, Yu Fan Chang, Chih Yi Chang, Han In Yang, Chia Wei Lin, Shaw Jenq Tsai, Jih Ing Chuang, Chia Ching Wu, Bu Miin Huang, H. Sunny Sun, Shang Hsun Yang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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, STHdh Q7/Q7 (WT) and STHdh Q111/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.

Original languageEnglish
Pages (from-to)605-617
Number of pages13
JournalCellular Physiology and Biochemistry
Volume48
Issue number2
DOIs
Publication statusPublished - 2018 Aug 1

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Fibroblast Growth Factor 9
Corpus Striatum
Huntington Disease
Cell Death
MAP Kinase Signaling System
Neuroprotective Agents
Neurodegenerative Diseases
Glial Cell Line-Derived Neurotrophic Factor
Western Blotting
Cell Proliferation
Fibroblast Growth Factors
Propidium
Starvation
Caspase 3
Transgenic Mice
Parkinson Disease
Cause of Death
Cell Survival
Alzheimer Disease
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

@article{f8b168e09ebe4706876a97e971ac40ea,
title = "Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease",
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, STHdh Q7/Q7 (WT) and STHdh Q111/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.",
author = "Yusuf, {Issa Olakunle} and Cheng, {Pei Hsun} and Chen, {Hsiu Mei} and Chang, {Yu Fan} and Chang, {Chih Yi} and Yang, {Han In} and Lin, {Chia Wei} and Tsai, {Shaw Jenq} and Chuang, {Jih Ing} and Wu, {Chia Ching} and Huang, {Bu Miin} and Sun, {H. Sunny} and Yang, {Shang Hsun}",
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Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease. / Yusuf, Issa Olakunle; Cheng, Pei Hsun; Chen, Hsiu Mei; Chang, Yu Fan; Chang, Chih Yi; Yang, Han In; Lin, Chia Wei; Tsai, Shaw Jenq; Chuang, Jih Ing; Wu, Chia Ching; Huang, Bu Miin; Sun, H. Sunny; Yang, Shang Hsun.

In: Cellular Physiology and Biochemistry, Vol. 48, No. 2, 01.08.2018, p. 605-617.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease

AU - Yusuf, Issa Olakunle

AU - Cheng, Pei Hsun

AU - Chen, Hsiu Mei

AU - Chang, Yu Fan

AU - Chang, Chih Yi

AU - Yang, Han In

AU - Lin, Chia Wei

AU - Tsai, Shaw Jenq

AU - Chuang, Jih Ing

AU - Wu, Chia Ching

AU - Huang, Bu Miin

AU - Sun, H. Sunny

AU - Yang, Shang Hsun

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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, STHdh Q7/Q7 (WT) and STHdh Q111/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.

AB - 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, STHdh Q7/Q7 (WT) and STHdh Q111/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.

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