Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice
Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH interventi...
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MDPI AG
2021-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/15/7974 |
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| author | Yu-Te Lin Yong-Shiou Lin Wen-Ling Cheng Jui-Chih Chang Yi-Chun Chao Chin-San Liu An-Chi Wei |
| author_facet | Yu-Te Lin Yong-Shiou Lin Wen-Ling Cheng Jui-Chih Chang Yi-Chun Chao Chin-San Liu An-Chi Wei |
| author_sort | Yu-Te Lin |
| collection | DOAJ |
| description | Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target. |
| first_indexed | 2024-03-10T09:15:15Z |
| format | Article |
| id | doaj.art-b1c6a133a341441d9f2a92f7c662058a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:15:15Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b1c6a133a341441d9f2a92f7c662058a2023-11-22T05:41:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012215797410.3390/ijms22157974Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic MiceYu-Te Lin0Yong-Shiou Lin1Wen-Ling Cheng2Jui-Chih Chang3Yi-Chun Chao4Chin-San Liu5An-Chi Wei6Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, TaiwanInstitute of ATP, Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50091, TaiwanInstitute of ATP, Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50091, TaiwanInstitute of ATP, Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50091, TaiwanInflammation Research & Drug Development Center, Changhua Christian Hospital, Changhua 50091, TaiwanInstitute of ATP, Vascular and Genomic Center, Changhua Christian Hospital, Changhua 50091, TaiwanGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, TaiwanSpinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target.https://www.mdpi.com/1422-0067/22/15/7974spinocerebellar ataxia type 3insulin-like growth factor 1RNA-seqcontext-specific metabolic networks |
| spellingShingle | Yu-Te Lin Yong-Shiou Lin Wen-Ling Cheng Jui-Chih Chang Yi-Chun Chao Chin-San Liu An-Chi Wei Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice International Journal of Molecular Sciences spinocerebellar ataxia type 3 insulin-like growth factor 1 RNA-seq context-specific metabolic networks |
| title | Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice |
| title_full | Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice |
| title_fullStr | Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice |
| title_full_unstemmed | Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice |
| title_short | Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice |
| title_sort | transcriptomic and metabolic network analysis of metabolic reprogramming and igf 1 modulation in sca3 transgenic mice |
| topic | spinocerebellar ataxia type 3 insulin-like growth factor 1 RNA-seq context-specific metabolic networks |
| url | https://www.mdpi.com/1422-0067/22/15/7974 |
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