A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke
IntroductionModification of the extracellular matrix (ECM) is one of the major processes in the pathology of brain damage following an ischemic stroke. However, our understanding of how age-related ECM alterations may affect stroke pathophysiology and its outcome is still very limited.MethodsWe cond...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1296455/full |
| _version_ | 1797447715923165184 |
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| author | Martina Chmelova Martina Chmelova Peter Androvic Denisa Kirdajova Jana Tureckova Jan Kriska Lukas Valihrach Lukas Valihrach Miroslava Anderova Lydia Vargova Lydia Vargova |
| author_facet | Martina Chmelova Martina Chmelova Peter Androvic Denisa Kirdajova Jana Tureckova Jan Kriska Lukas Valihrach Lukas Valihrach Miroslava Anderova Lydia Vargova Lydia Vargova |
| author_sort | Martina Chmelova |
| collection | DOAJ |
| description | IntroductionModification of the extracellular matrix (ECM) is one of the major processes in the pathology of brain damage following an ischemic stroke. However, our understanding of how age-related ECM alterations may affect stroke pathophysiology and its outcome is still very limited.MethodsWe conducted an ECM-targeted re-analysis of our previously obtained RNA-Seq dataset of aging, ischemic stroke and their interactions in young adult (3-month-old) and aged (18-month-old) mice. The permanent middle cerebral artery occlusion (pMCAo) in rodents was used as a model of ischemic stroke. Altogether 56 genes of interest were chosen for this study.ResultsWe identified an increased activation of the genes encoding proteins related to ECM degradation, such as matrix metalloproteinases (MMPs), proteases of a disintegrin and metalloproteinase with the thrombospondin motifs (ADAMTS) family and molecules that regulate their activity, tissue inhibitors of metalloproteinases (TIMPs). Moreover, significant upregulation was also detected in the mRNA of other ECM molecules, such as proteoglycans, syndecans and link proteins. Notably, we identified 8 genes where this upregulation was enhanced in aged mice in comparison with the young ones. Ischemia evoked a significant downregulation in only 6 of our genes of interest, including those encoding proteins associated with the protective function of ECM molecules (e.g., brevican, Hapln4, Sparcl1); downregulation in brevican was more prominent in aged mice. The study was expanded by proteome analysis, where we observed an ischemia-induced overexpression in three proteins, which are associated with neuroinflammation (fibronectin and vitronectin) and neurodegeneration (link protein Hapln2). In fibronectin and Hapln2, this overexpression was more pronounced in aged post-ischemic animals.ConclusionBased on these results, we can conclude that the ratio between the protecting and degrading mechanisms in the aged brain is shifted toward degradation and contributes to the aged tissues’ increased sensitivity to ischemic insults. Altogether, our data provide fresh perspectives on the processes underlying ischemic injury in the aging brain and serve as a freely accessible resource for upcoming research. |
| first_indexed | 2024-03-09T13:59:56Z |
| format | Article |
| id | doaj.art-6b7a09d149be46f69fa671ac67a7ed87 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-09T13:59:56Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-6b7a09d149be46f69fa671ac67a7ed872023-11-30T08:26:16ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-11-011710.3389/fncel.2023.12964551296455A view of the genetic and proteomic profile of extracellular matrix molecules in aging and strokeMartina Chmelova0Martina Chmelova1Peter Androvic2Denisa Kirdajova3Jana Tureckova4Jan Kriska5Lukas Valihrach6Lukas Valihrach7Miroslava Anderova8Lydia Vargova9Lydia Vargova10Department of Neuroscience, Second Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Gene Expression, Institute of Biotechnology of the Czech Academy of Sciences – BIOCEV, Vestec, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaLaboratory of Gene Expression, Institute of Biotechnology of the Czech Academy of Sciences – BIOCEV, Vestec, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaDepartment of Neuroscience, Second Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, CzechiaIntroductionModification of the extracellular matrix (ECM) is one of the major processes in the pathology of brain damage following an ischemic stroke. However, our understanding of how age-related ECM alterations may affect stroke pathophysiology and its outcome is still very limited.MethodsWe conducted an ECM-targeted re-analysis of our previously obtained RNA-Seq dataset of aging, ischemic stroke and their interactions in young adult (3-month-old) and aged (18-month-old) mice. The permanent middle cerebral artery occlusion (pMCAo) in rodents was used as a model of ischemic stroke. Altogether 56 genes of interest were chosen for this study.ResultsWe identified an increased activation of the genes encoding proteins related to ECM degradation, such as matrix metalloproteinases (MMPs), proteases of a disintegrin and metalloproteinase with the thrombospondin motifs (ADAMTS) family and molecules that regulate their activity, tissue inhibitors of metalloproteinases (TIMPs). Moreover, significant upregulation was also detected in the mRNA of other ECM molecules, such as proteoglycans, syndecans and link proteins. Notably, we identified 8 genes where this upregulation was enhanced in aged mice in comparison with the young ones. Ischemia evoked a significant downregulation in only 6 of our genes of interest, including those encoding proteins associated with the protective function of ECM molecules (e.g., brevican, Hapln4, Sparcl1); downregulation in brevican was more prominent in aged mice. The study was expanded by proteome analysis, where we observed an ischemia-induced overexpression in three proteins, which are associated with neuroinflammation (fibronectin and vitronectin) and neurodegeneration (link protein Hapln2). In fibronectin and Hapln2, this overexpression was more pronounced in aged post-ischemic animals.ConclusionBased on these results, we can conclude that the ratio between the protecting and degrading mechanisms in the aged brain is shifted toward degradation and contributes to the aged tissues’ increased sensitivity to ischemic insults. Altogether, our data provide fresh perspectives on the processes underlying ischemic injury in the aging brain and serve as a freely accessible resource for upcoming research.https://www.frontiersin.org/articles/10.3389/fncel.2023.1296455/fullextracellular matrixstrokeaginggenesproteins |
| spellingShingle | Martina Chmelova Martina Chmelova Peter Androvic Denisa Kirdajova Jana Tureckova Jan Kriska Lukas Valihrach Lukas Valihrach Miroslava Anderova Lydia Vargova Lydia Vargova A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke Frontiers in Cellular Neuroscience extracellular matrix stroke aging genes proteins |
| title | A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| title_full | A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| title_fullStr | A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| title_full_unstemmed | A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| title_short | A view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| title_sort | view of the genetic and proteomic profile of extracellular matrix molecules in aging and stroke |
| topic | extracellular matrix stroke aging genes proteins |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1296455/full |
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