The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis
Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological inte...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12934 |
| _version_ | 1797507720432058368 |
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| author | Mohammad-Masoud Zavvarian Cindy Zhou Sabah Kahnemuyipour James Hong Michael G. Fehlings |
| author_facet | Mohammad-Masoud Zavvarian Cindy Zhou Sabah Kahnemuyipour James Hong Michael G. Fehlings |
| author_sort | Mohammad-Masoud Zavvarian |
| collection | DOAJ |
| description | Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of <i>Fn1</i> and <i>Jun</i> with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance. |
| first_indexed | 2024-03-10T04:52:27Z |
| format | Article |
| id | doaj.art-922214ed30894e02ae0fe073671c00fc |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:27Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-922214ed30894e02ae0fe073671c00fc2023-11-23T02:30:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231293410.3390/ijms222312934The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional AnalysisMohammad-Masoud Zavvarian0Cindy Zhou1Sabah Kahnemuyipour2James Hong3Michael G. Fehlings4Division of Genetics and Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, CanadaDivision of Genetics and Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, CanadaHuman Biology Department, University of Toronto, Toronto, ON M5S 3J6, CanadaDivision of Genetics and Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, CanadaDivision of Genetics and Development, Krembil Brain Institute, University Health Network, Toronto, ON M5T 2S8, CanadaDespite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of <i>Fn1</i> and <i>Jun</i> with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance.https://www.mdpi.com/1422-0067/22/23/12934spinal cord injurymicroarraycross-species comparisontranscriptional analysis |
| spellingShingle | Mohammad-Masoud Zavvarian Cindy Zhou Sabah Kahnemuyipour James Hong Michael G. Fehlings The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis International Journal of Molecular Sciences spinal cord injury microarray cross-species comparison transcriptional analysis |
| title | The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis |
| title_full | The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis |
| title_fullStr | The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis |
| title_full_unstemmed | The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis |
| title_short | The MAPK Signaling Pathway Presents Novel Molecular Targets for Therapeutic Intervention after Traumatic Spinal Cord Injury: A Comparative Cross-Species Transcriptional Analysis |
| title_sort | mapk signaling pathway presents novel molecular targets for therapeutic intervention after traumatic spinal cord injury a comparative cross species transcriptional analysis |
| topic | spinal cord injury microarray cross-species comparison transcriptional analysis |
| url | https://www.mdpi.com/1422-0067/22/23/12934 |
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