Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions
Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients’ skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidros...
Autores Principales: | , , , , |
---|---|
Formato: | Artículo (Article) |
Lenguaje: | Inglés (English) |
Publicado: |
Blackwell Publishing Ltd
2018
|
Materias: | |
Acceso en línea: | https://repository.urosario.edu.co/handle/10336/24032 https://doi.org/10.1111/exd.13532 |
id |
ir-10336-24032 |
---|---|
recordtype |
dspace |
spelling |
ir-10336-240322022-05-02T12:37:17Z Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions Valero-Rubio D. Jiménez K.M. Fonseca-Mendoza, Dora Janeth Payan-Gomez, Cesar Laissue P. Alpha levo fucosidase Rna Small interfering rna Transcription factor Alpha levo fucosidase Transcriptome Article Bioinformatics Cell differentiation Controlled study Down regulation Epidermis Fuca1 gene Fucosidosis Gene cluster Gene expression Gene mutation Gene silencing Hacat cell line Hemangiokeratoma Histogenesis Human Human cell Immune response Keratinocyte Molecular mechanics Pathogenesis Polymerase chain reaction Protein expression Quantitative analysis Reverse transcription polymerase chain reaction Rna extraction Skin defect Transcriptomics Upregulation Biology Cell line Complication Dna microarray Fucosidosis Gene expression profiling Gene knockdown Genetics Hemangiokeratoma Immunology Keratinocyte Skin disease Alpha-l-fucosidase Angiokeratoma Cell differentiation Cell line Computational biology Down-regulation Epidermis Fucosidosis Gene expression profiling Gene knockdown techniques Humans Keratinocytes Oligonucleotide array sequence analysis Skin diseases Transcriptome Up-regulation Angiokeratoma Foxn1 Lysosomal alpha-l-fucosidase Skin disease Transcriptome human development and aging Fuca1 protein Growth Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients’ skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations. Obtaining samples for functional studies has been challenging due to the inherent difficulty in finding affected individuals. The effect of FUCA1 dysfunction on gene expression is unknown. The aim of this study was to analyse, in keratinocytes, the transcriptomic effect of FUCA1 knock-down for a better understanding of skin lesions’ pathogenesis affecting fucosidosis patients. FUCA1 knock-down (siRNA) was performed in human HaCaT immortalised keratinocytes. Affymetrix arrays and qPCR were used for analysing gene expression. Bioinformatics was used for functional clustering of modified genes. In total, 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Up-regulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n = 17) and immune response (n = 61). Several transcription factors were up-regulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, that is FOXN1. We thus propose that fucosidosis-related skin lesions (eg angiokeratoma) and those of other diseases (eg psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades. © 2018 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd 2018 2020-05-26T00:07:48Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 16000625 09066705 https://repository.urosario.edu.co/handle/10336/24032 https://doi.org/10.1111/exd.13532 eng info:eu-repo/semantics/openAccess application/pdf Blackwell Publishing Ltd instname:Universidad del Rosario |
institution |
EdocUR - Universidad del Rosario |
collection |
DSpace |
language |
Inglés (English) |
topic |
Alpha levo fucosidase Rna Small interfering rna Transcription factor Alpha levo fucosidase Transcriptome Article Bioinformatics Cell differentiation Controlled study Down regulation Epidermis Fuca1 gene Fucosidosis Gene cluster Gene expression Gene mutation Gene silencing Hacat cell line Hemangiokeratoma Histogenesis Human Human cell Immune response Keratinocyte Molecular mechanics Pathogenesis Polymerase chain reaction Protein expression Quantitative analysis Reverse transcription polymerase chain reaction Rna extraction Skin defect Transcriptomics Upregulation Biology Cell line Complication Dna microarray Fucosidosis Gene expression profiling Gene knockdown Genetics Hemangiokeratoma Immunology Keratinocyte Skin disease Alpha-l-fucosidase Angiokeratoma Cell differentiation Cell line Computational biology Down-regulation Epidermis Fucosidosis Gene expression profiling Gene knockdown techniques Humans Keratinocytes Oligonucleotide array sequence analysis Skin diseases Transcriptome Up-regulation Angiokeratoma Foxn1 Lysosomal alpha-l-fucosidase Skin disease Transcriptome human development and aging Fuca1 protein Growth |
spellingShingle |
Alpha levo fucosidase Rna Small interfering rna Transcription factor Alpha levo fucosidase Transcriptome Article Bioinformatics Cell differentiation Controlled study Down regulation Epidermis Fuca1 gene Fucosidosis Gene cluster Gene expression Gene mutation Gene silencing Hacat cell line Hemangiokeratoma Histogenesis Human Human cell Immune response Keratinocyte Molecular mechanics Pathogenesis Polymerase chain reaction Protein expression Quantitative analysis Reverse transcription polymerase chain reaction Rna extraction Skin defect Transcriptomics Upregulation Biology Cell line Complication Dna microarray Fucosidosis Gene expression profiling Gene knockdown Genetics Hemangiokeratoma Immunology Keratinocyte Skin disease Alpha-l-fucosidase Angiokeratoma Cell differentiation Cell line Computational biology Down-regulation Epidermis Fucosidosis Gene expression profiling Gene knockdown techniques Humans Keratinocytes Oligonucleotide array sequence analysis Skin diseases Transcriptome Up-regulation Angiokeratoma Foxn1 Lysosomal alpha-l-fucosidase Skin disease Transcriptome human development and aging Fuca1 protein Growth Valero-Rubio D. Jiménez K.M. Fonseca-Mendoza, Dora Janeth Payan-Gomez, Cesar Laissue P. Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
description |
Fucosidosis is a rare lysosomal storage disease which has been classified into two subtypes, depending on the severity of clinical signs and symptoms. Fucosidosis patients’ skin abnormalities include angiokeratoma corporis diffusum, widespread telangiectasia, thick skin, hyperhidrosis and hypohidrosis, acrocyanosis and distal transverse nail bands. It has been described that >50% of fucosidosis patients have angiokeratoma. At molecular level, fucosidosis is caused by lysosomal alpha-L-fucosidase (FUCA1) gene mutations. Obtaining samples for functional studies has been challenging due to the inherent difficulty in finding affected individuals. The effect of FUCA1 dysfunction on gene expression is unknown. The aim of this study was to analyse, in keratinocytes, the transcriptomic effect of FUCA1 knock-down for a better understanding of skin lesions’ pathogenesis affecting fucosidosis patients. FUCA1 knock-down (siRNA) was performed in human HaCaT immortalised keratinocytes. Affymetrix arrays and qPCR were used for analysing gene expression. Bioinformatics was used for functional clustering of modified genes. In total, 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Up-regulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n = 17) and immune response (n = 61). Several transcription factors were up-regulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, that is FOXN1. We thus propose that fucosidosis-related skin lesions (eg angiokeratoma) and those of other diseases (eg psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades. © 2018 John Wiley and Sons A/S. Published by John Wiley and Sons Ltd |
format |
Artículo (Article) |
author |
Valero-Rubio D. Jiménez K.M. Fonseca-Mendoza, Dora Janeth Payan-Gomez, Cesar Laissue P. |
author_facet |
Valero-Rubio D. Jiménez K.M. Fonseca-Mendoza, Dora Janeth Payan-Gomez, Cesar Laissue P. |
author_sort |
Valero-Rubio D. |
title |
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
title_short |
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
title_full |
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
title_fullStr |
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
title_full_unstemmed |
Transcriptomic analysis of FUCA1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
title_sort |
transcriptomic analysis of fuca1 knock-down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions |
publisher |
Blackwell Publishing Ltd |
publishDate |
2018 |
url |
https://repository.urosario.edu.co/handle/10336/24032 https://doi.org/10.1111/exd.13532 |
_version_ |
1740172270250229760 |
score |
12,131701 |