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...

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Autores:
Tipo de recurso:
Fecha de publicación:
2018
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/24032
Acceso en línea:
https://doi.org/10.1111/exd.13532
https://repository.urosario.edu.co/handle/10336/24032
Palabra clave:
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
Rights
License
Abierto (Texto Completo)
Description
Summary: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