Transcriptomic analysis of FUCA1 knockdown in keratinocytes reveals new insights in the pathogenesis of fucosidosis skin lesions.

Cesar Ernesto Payan Gomez, Danyela Valero rubio, Karen Jimenez , Dora Janeth Fonseca , Paul Laissue Hormaza

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 the present 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. 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Upregulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n=17) and immune response (n= 61). Several transcription factors were upregulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, i.e. FOXN1. We thus propose that fucosidosis-related skin lesions (e.g. angiokeratoma) and those of other diseases (e.g. psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.
Original languageEnglish (US)
Article number1
Pages (from-to)1-6
Number of pages6
JournalExperimental Dermatology
DOIs
StatePublished - Mar 8 2018

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Fucosidosis
Keratinocytes
Skin
Genes
Angiokeratoma
Gene expression
Small Interfering RNA
Transcription Factors
alpha-L-Fucosidase
Nails
Bioinformatics
Hypohidrosis
Skin Abnormalities
Lysosomal Storage Diseases
Hyperhidrosis
Fabry Disease
Gene Expression
Telangiectasis
Computational Biology
Psoriasis

Cite this

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title = "Transcriptomic analysis of FUCA1 knockdown in keratinocytes reveals new insights in the pathogenesis of fucosidosis skin lesions.",
abstract = "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 the present 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. 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Upregulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n=17) and immune response (n= 61). Several transcription factors were upregulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, i.e. FOXN1. We thus propose that fucosidosis-related skin lesions (e.g. angiokeratoma) and those of other diseases (e.g. psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.",
author = "{Payan Gomez}, {Cesar Ernesto} and rubio, {Danyela Valero} and Karen Jimenez and Fonseca, {Dora Janeth} and {Laissue Hormaza}, Paul",
year = "2018",
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doi = "10.1111/exd.13532",
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journal = "Experimental Dermatology",
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Transcriptomic analysis of FUCA1 knockdown in keratinocytes reveals new insights in the pathogenesis of fucosidosis skin lesions. / Payan Gomez, Cesar Ernesto; rubio, Danyela Valero ; Jimenez , Karen ; Fonseca , Dora Janeth ; Laissue Hormaza, Paul.

In: Experimental Dermatology, 08.03.2018, p. 1-6.

Research output: Contribution to journalArticle

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AU - rubio, Danyela Valero

AU - Jimenez , Karen

AU - Fonseca , Dora Janeth

AU - Laissue Hormaza, Paul

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N2 - 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 the present 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. 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Upregulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n=17) and immune response (n= 61). Several transcription factors were upregulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, i.e. FOXN1. We thus propose that fucosidosis-related skin lesions (e.g. angiokeratoma) and those of other diseases (e.g. psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.

AB - 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 the present 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. 387 genes showed differential expression between FUCA1 silenced and non-silenced cells (222 up-regulated and 165 down-regulated). Upregulated genes belonged to two major groups: keratinocyte differentiation/epidermal development (n=17) and immune response (n= 61). Several transcription factors were upregulated in FUCA1-siRNA transfected cells. This effect might partly have been produced by abnormal transcription factor expression, i.e. FOXN1. We thus propose that fucosidosis-related skin lesions (e.g. angiokeratoma) and those of other diseases (e.g. psoriasis) might be caused by dysfunctions in common aetiological overlapping molecular cascades.

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