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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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Autores principales: Rintz, Estera, Gaffke, Lidia, Podlacha, Magdalena, Brokowska, Joanna, Cyske, Zuzanna, Węgrzyn, Grzegorz, Pierzynowska, Karolina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246638/
https://www.ncbi.nlm.nih.gov/pubmed/32366041
http://dx.doi.org/10.3390/ijms21093194
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author Rintz, Estera
Gaffke, Lidia
Podlacha, Magdalena
Brokowska, Joanna
Cyske, Zuzanna
Węgrzyn, Grzegorz
Pierzynowska, Karolina
author_facet Rintz, Estera
Gaffke, Lidia
Podlacha, Magdalena
Brokowska, Joanna
Cyske, Zuzanna
Węgrzyn, Grzegorz
Pierzynowska, Karolina
author_sort Rintz, Estera
collection PubMed
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 CD9, CLU, MME 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.
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spelling pubmed-72466382020-06-10 Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses Rintz, Estera Gaffke, Lidia Podlacha, Magdalena Brokowska, Joanna Cyske, Zuzanna Węgrzyn, Grzegorz Pierzynowska, Karolina Int J Mol Sci Article 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 CD9, CLU, MME 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. MDPI 2020-04-30 /pmc/articles/PMC7246638/ /pubmed/32366041 http://dx.doi.org/10.3390/ijms21093194 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rintz, Estera
Gaffke, Lidia
Podlacha, Magdalena
Brokowska, Joanna
Cyske, Zuzanna
Węgrzyn, Grzegorz
Pierzynowska, Karolina
Transcriptomic Changes Related to Cellular Processes with Particular Emphasis on Cell Activation in Lysosomal Storage Diseases from the Group of Mucopolysaccharidoses
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246638/
https://www.ncbi.nlm.nih.gov/pubmed/32366041
http://dx.doi.org/10.3390/ijms21093194
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