Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels
Background: Mucopolysaccharidosis (MPS) is a class of hereditary metabolic diseases that demonstrate itself by accumulating incompletely degraded glycosaminoglycans (GAGs). MPS are classified according to the kind(s) of stored GAG(s) and specific genetic/enzymatic defects. Despite...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2024-12-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912415 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846100266762371072 |
|---|---|
| author | Karolina Wiśniewska Magdalena Żabińska Lidia Gaffke Aneta Szulc Beata M. Walter Grzegorz Węgrzyn Karolina Pierzynowska |
| author_facet | Karolina Wiśniewska Magdalena Żabińska Lidia Gaffke Aneta Szulc Beata M. Walter Grzegorz Węgrzyn Karolina Pierzynowska |
| author_sort | Karolina Wiśniewska |
| collection | DOAJ |
| description | Background: Mucopolysaccharidosis (MPS) is a class of hereditary metabolic diseases that demonstrate itself by accumulating incompletely degraded glycosaminoglycans (GAGs). MPS are classified according to the kind(s) of stored GAG(s) and specific genetic/enzymatic defects. Despite the accumulation of the same type of GAG, two MPS diseases, Sanfilippo (MPS III) and Morquio (MPS IV), are further distinguished into subclasses based on different enzymes that are deficient. Although genetic defects in MPS are known, molecular mechanisms of particular MPS types are still incomplete. This work aimed to investigate gene expression patterns in MPS III and MPS IV subtypes to identify dysregulated genes that could indicate unidentified molecular mechanisms of the diseases. Methods: Transcriptomic analyses were conducted to assess gene expression patterns in MPS and control cells. Western blotting and immunohistochemistry determined selected protein levels (products of the most significantly dysregulated genes). Effects of decreased levels of gene expression were investigated using small interferring RNA (siRNA)-mediated gene silencing. Results: Transcriptomic analyses indicated 45 commonly dysregulated genes among all MPS III subtypes and as many as 150 commonly dysregulated genes among both MPS IV subtypes. A few genes revealed particularly high levels of dysregulation, including PFN1, MFAP5, and MMP12. Intriguingly, elevated levels of profilin-1 (product of the PFN1 gene) could be reduced by decreasing GAG levels in genistein-treated MPS III and MPS IV cells, while silencing of PFN1 caused a significant decrease in GAG accumulation in these cells, indicating an interdependent correlation between profilin-1 and GAG levels. Conclusions: A plethora of commonly dysregulated genes were identified in MPS subtypes III and IV. Some of these genes, like PFN1, MFAP5, and MMP12, revealed highly pronounced changes in expression relative to control cells. An interdependent correlation between GAG levels and the expression of the PFN1 gene was identified. Thus, PFN1 could be suggested as a potential new therapeutic target for MPS III and IV. |
| format | Article |
| id | doaj-art-a0161de0a07b49d1a5914d08beff496f |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-a0161de0a07b49d1a5914d08beff496f2024-12-30T11:39:30ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-12-01291241510.31083/j.fbl2912415S2768-6701(24)01546-6Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan LevelsKarolina Wiśniewska0Magdalena Żabińska1Lidia Gaffke2Aneta Szulc3Beata M. Walter4Grzegorz Węgrzyn5Karolina Pierzynowska6Department of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandStructural Biology Laboratory, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandDepartment of Molecular Biology, Faculty of Biology, University of Gdansk, 80-308 Gdansk, PolandBackground: Mucopolysaccharidosis (MPS) is a class of hereditary metabolic diseases that demonstrate itself by accumulating incompletely degraded glycosaminoglycans (GAGs). MPS are classified according to the kind(s) of stored GAG(s) and specific genetic/enzymatic defects. Despite the accumulation of the same type of GAG, two MPS diseases, Sanfilippo (MPS III) and Morquio (MPS IV), are further distinguished into subclasses based on different enzymes that are deficient. Although genetic defects in MPS are known, molecular mechanisms of particular MPS types are still incomplete. This work aimed to investigate gene expression patterns in MPS III and MPS IV subtypes to identify dysregulated genes that could indicate unidentified molecular mechanisms of the diseases. Methods: Transcriptomic analyses were conducted to assess gene expression patterns in MPS and control cells. Western blotting and immunohistochemistry determined selected protein levels (products of the most significantly dysregulated genes). Effects of decreased levels of gene expression were investigated using small interferring RNA (siRNA)-mediated gene silencing. Results: Transcriptomic analyses indicated 45 commonly dysregulated genes among all MPS III subtypes and as many as 150 commonly dysregulated genes among both MPS IV subtypes. A few genes revealed particularly high levels of dysregulation, including PFN1, MFAP5, and MMP12. Intriguingly, elevated levels of profilin-1 (product of the PFN1 gene) could be reduced by decreasing GAG levels in genistein-treated MPS III and MPS IV cells, while silencing of PFN1 caused a significant decrease in GAG accumulation in these cells, indicating an interdependent correlation between profilin-1 and GAG levels. Conclusions: A plethora of commonly dysregulated genes were identified in MPS subtypes III and IV. Some of these genes, like PFN1, MFAP5, and MMP12, revealed highly pronounced changes in expression relative to control cells. An interdependent correlation between GAG levels and the expression of the PFN1 gene was identified. Thus, PFN1 could be suggested as a potential new therapeutic target for MPS III and IV.https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912415mucopolysaccharidosesprofilin-1pfn1glycosaminoglycanssanfilippo diseasemorquio disease |
| spellingShingle | Karolina Wiśniewska Magdalena Żabińska Lidia Gaffke Aneta Szulc Beata M. Walter Grzegorz Węgrzyn Karolina Pierzynowska Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels Frontiers in Bioscience-Landmark mucopolysaccharidoses profilin-1 pfn1 glycosaminoglycans sanfilippo disease morquio disease |
| title | Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels |
| title_full | Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels |
| title_fullStr | Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels |
| title_full_unstemmed | Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels |
| title_short | Shared Gene Expression Dysregulation Across Subtypes of Sanfilippo and Morquio Diseases: The Role of PFN1 in Regulating Glycosaminoglycan Levels |
| title_sort | shared gene expression dysregulation across subtypes of sanfilippo and morquio diseases the role of pfn1 in regulating glycosaminoglycan levels |
| topic | mucopolysaccharidoses profilin-1 pfn1 glycosaminoglycans sanfilippo disease morquio disease |
| url | https://www.imrpress.com/journal/FBL/29/12/10.31083/j.fbl2912415 |
| work_keys_str_mv | AT karolinawisniewska sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT magdalenazabinska sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT lidiagaffke sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT anetaszulc sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT beatamwalter sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT grzegorzwegrzyn sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels AT karolinapierzynowska sharedgeneexpressiondysregulationacrosssubtypesofsanfilippoandmorquiodiseasestheroleofpfn1inregulatingglycosaminoglycanlevels |