Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses
Although mucopolysaccharidoses (MPS), inherited metabolic diseases from the group of lysosomal storage diseases (LSD), are monogenic disorders, recent studies indicated that their molecular mechanisms are complicated. Storage of glycosaminoglycans (GAGs), arising from a deficiency in one of the enzy...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3194 |
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| author | Estera Rintz Lidia Gaffke Magdalena Podlacha Joanna Brokowska Zuzanna Cyske Grzegorz Węgrzyn Karolina Pierzynowska |
| author_facet | Estera Rintz Lidia Gaffke Magdalena Podlacha Joanna Brokowska Zuzanna Cyske Grzegorz Węgrzyn Karolina Pierzynowska |
| author_sort | Estera Rintz |
| collection | DOAJ |
| description | Although mucopolysaccharidoses (MPS), inherited metabolic diseases from the group of lysosomal storage diseases (LSD), are monogenic disorders, recent studies indicated that their molecular mechanisms are complicated. Storage of glycosaminoglycans (GAGs), arising from a deficiency in one of the enzymes involved in the degradation of these compounds, is the primary cause of each MPS type. However, dysfunctions of various cellular organelles and disturbance of cellular processes have been reported which contribute considerably to pathomechanisms of the disease. Here, we present a complex transcriptomic analysis in which all types and subtypes of MPS were investigated, with special emphasis on genes related to cell activation processes. Complex changes in expression of these genes were found in fibroblasts of all MPS types, with number of transcripts revealing higher or lower levels (relative to control fibroblasts) between 19 and over 50, depending on MPS type. Genes in which expression was significantly affected in most MPS types code for proteins involved in following processes, classified according to Gene Ontology knowledge database: cell activation, cell growth, cell recognition, and cell division. Levels of some transcripts (including <i>CD9, CLU, MME</i> and others) were especially significantly changed (over five times relative to controls). Our results are discussed in the light of molecular pathomechanisms of MPS, indicating that secondary and/or tertiary changes, relative to GAG storage, might significantly modulate cellular dysfunctions and contribute to molecular mechanisms of the disease. This may influence the efficacy of various therapies and suggests why various treatments are not fully effective in improving the complex symptoms of MPS. |
| first_indexed | 2024-03-10T20:07:47Z |
| format | Article |
| id | doaj.art-b76056414f694f8498c927a8f293963a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:07:47Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b76056414f694f8498c927a8f293963a2023-11-19T23:11:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219319410.3390/ijms21093194Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of MucopolysaccharidosesEstera Rintz0Lidia Gaffke1Magdalena Podlacha2Joanna Brokowska3Zuzanna Cyske4Grzegorz Węgrzyn5Karolina Pierzynowska6Department of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandDepartment of Molecular Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, PolandAlthough mucopolysaccharidoses (MPS), inherited metabolic diseases from the group of lysosomal storage diseases (LSD), are monogenic disorders, recent studies indicated that their molecular mechanisms are complicated. Storage of glycosaminoglycans (GAGs), arising from a deficiency in one of the enzymes involved in the degradation of these compounds, is the primary cause of each MPS type. However, dysfunctions of various cellular organelles and disturbance of cellular processes have been reported which contribute considerably to pathomechanisms of the disease. Here, we present a complex transcriptomic analysis in which all types and subtypes of MPS were investigated, with special emphasis on genes related to cell activation processes. Complex changes in expression of these genes were found in fibroblasts of all MPS types, with number of transcripts revealing higher or lower levels (relative to control fibroblasts) between 19 and over 50, depending on MPS type. Genes in which expression was significantly affected in most MPS types code for proteins involved in following processes, classified according to Gene Ontology knowledge database: cell activation, cell growth, cell recognition, and cell division. Levels of some transcripts (including <i>CD9, CLU, MME</i> and others) were especially significantly changed (over five times relative to controls). Our results are discussed in the light of molecular pathomechanisms of MPS, indicating that secondary and/or tertiary changes, relative to GAG storage, might significantly modulate cellular dysfunctions and contribute to molecular mechanisms of the disease. This may influence the efficacy of various therapies and suggests why various treatments are not fully effective in improving the complex symptoms of MPS.https://www.mdpi.com/1422-0067/21/9/3194cell activationmucopolysaccharidosesgene expressiontranscriptomics |
| spellingShingle | Estera Rintz Lidia Gaffke Magdalena Podlacha Joanna Brokowska Zuzanna Cyske Grzegorz Węgrzyn Karolina Pierzynowska Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses International Journal of Molecular Sciences cell activation mucopolysaccharidoses gene expression transcriptomics |
| title | Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses |
| title_full | Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses |
| title_fullStr | Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses |
| title_full_unstemmed | Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses |
| title_short | Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses |
| title_sort | transcriptomic changes related to cellular processes with particular emphasis on cell activation in lysosomal storage diseases from the group of mucopolysaccharidoses |
| topic | cell activation mucopolysaccharidoses gene expression transcriptomics |
| url | https://www.mdpi.com/1422-0067/21/9/3194 |
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