Transcriptomic analysis of <i><scp>FUCA</scp>1</i> knock‐down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions

Valero-Rubio, Danyela; Jiménez, Karen M.; Fonseca, Dora Janeth; Payán‐Gómez, César; Laissue, Paul

doi:10.1111/exd.13532

Cited by 7 publications

(6 citation statements)

References 41 publications

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“…We were also able to capture downregulations of lysosomal enzymes such as FUCA1 and GALNS involved with keratinocyte differentiation, 34,35 and lipid biosynthesis/trafficking 48 . Also, we detected a decreased expression of AZGP which is correlated with abnormalities in lipid metabolism.…”

Section: Discussionmentioning

confidence: 74%

“…We were able to detect even from non‐lesional AD, significant variation on lipid metabolism‐related enzymes compared with HCs. The cellular mediators, tissue alpha‐L‐fucosidase (FUCA1), zinc‐alpha‐2‐glycoprotein (AZGP) and N‐acetylgalactosamine‐6‐sulfatase (GALNS) have been found significantly downregulated in AD 34,35 . In particular, we assessed down‐expression of 7‐dehydrocholesterol reductase (DHCR7) and ester hydrolase (C11orf54).…”

Section: Resultsmentioning

confidence: 99%

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Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Morelli

Gaspari

Gabriele

et al. 2021

Experimental Dermatology

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Atopic Dermatitis (AD) is a common inflammatory skin disease characterized by skin and systemic inflammation, and barrier dysfunction. Herein, we investigate the proteomic profile of AD skin barrier to identify a unique signature with an easy‐performed sampling approach. We enrolled 8 moderate‐to‐severe AD patients and 8 age‐ and gender‐matched healthy controls. Swabs were obtained from non‐lesional skin of retroauricular area and antecubital fold. Peptide mixtures obtained through protein precipitation and in‐solution digestion were analysed using NanoLC‐MS/MS. Label‐free quantification and statistical analysis were conducted in MaxQuant and Perseus. Bioinformatics analysis was performed using Gene Ontology and STRING. We identified 908 proteins and 35 differentially expressed proteins were selected (fold change 2, FDR < 0.05). Particularly, AD skin showed downregulation of skin hydration factors, structural and epidermal proteins, abnormalities in protease‐proteasome complex and lipid metabolism profile. Imbalance of antioxidant and inflammatory processes, along with TDRD15 upregulation was also observed. Our result showed partial overlap with skin biopsy/tape‐strips studies, showing the reliability of our sampling approach which could be an easier method of detection of hallmark barrier proteins in AD. Furthermore, we displayed a new differentially expressed set of proteins, not yet explored in AD which can have a potential role in AD pathomechanisms.

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Section: Discussionmentioning

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Morelli

Gaspari

Gabriele

et al. 2021

Experimental Dermatology

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“…We identified several proteins in MIH saliva associated with skin-abnormalities caused by chronic inflammation. For example, FUCA1 is a carbohydrate degrading enzyme and FUCA1 gene-mutations are linked to fucosidosis that causes severe skin abnormalities due to disturbed carbohydrate metabolism 55 . The human kallikrein 8 protein (KLK8) is expressed in many normal tissues including the salivary gland 56 .…”

Section: Discussionmentioning

confidence: 99%

Saliva proteomic patterns in patients with molar incisor hypomineralization

Bekes

Mitulović

Meißner³

et al. 2020

Sci Rep

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Molar incisor hypomineralization (MiH) is an endemic pediatric disease with an unclear pathogenesis. considering that saliva controls enamel remineralization and that MiH is associated with higher saliva flow rate, we hypothesized that the protein composition of saliva is linked to disease. To test this, we enrolled 5 children aged 6-14 years with MIH showing at least one hypersensitive molar and 5 cariesfree children without hypomineralization. Saliva samples were subjected to proteomic analysis followed by protein classification in to biological pathways. Among 618 salivary proteins identified with high confidence, 88 proteins were identified exclusively in MIH patients and 16 proteins in healthy controls only. Biological pathway analysis classified these 88 patient-only proteins to neutrophil-mediated adaptive immunity, the activation of the classical pathway of complement activation, extracellular matrix degradation, heme scavenging as well as glutathione-and drug metabolism. The 16 controlsonly proteins were associated with adaptive immunity related to platelet degranulation and the lysosome. This report suggests that the proteaneous composition of saliva is affected in MIH patients, reflecting a catabolic environment which is linked to inflammation. The term molar incisor hypomineralization (MIH) was coined in 2001 and defines a qualitative enamel defect affecting one or more first permanent molars with or without the involvement of permanent incisors 1. The global prevalence of MIH exceeds one-tenth of children, ranging from 0.5% to 40.2% and differing between countries 2. Demarcated hypomineralized enamel lesions are caused by the process of amelogenesis being altered or interrupted 3. Compared to normal teeth, affected enamel is characterized by a reduction in mineral quantity and quality, increased porosity and reduced hardness 4. The clinical management of MIH is challenging because of rapid wear, progressing enamel loss, increased susceptibility to caries, loss of fillings, and severe hypersensitivity 5. Although MIH is a pandemic pediatric disease, the etiology remains unknown 6. Several hypotheses are proposed, including childhood illness, genetic influences 7,8 , and a putative individual threshold of susceptibility 3. Thus, there is an increasing demand to better understand the cause and consequence(s) of MIH at the cellular and molecular level. Chronic subclinical pulpal inflammation is a consequence of increased enamel porosity and reduced hardness in MIH 9. Pulpitis is characterized by enhanced neutrophil emigration into the pulp tissue 10,11 and biomarkers can be identified in gingival crevicular fluid 12. Moreover, in periodontitis patients, neutrophils constantly migrate through the oral epithelia into the saliva 13 , with increasing numbers exhibiting apoptosis and augmented levels of degranulation markers 14. Further, saliva of MIH patients reportedly displays altered physicochemical properties such as altered flow rates, viscosity, pH and acid buffering capacity 15. Thus, it is conceivabl...

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“…Fucosidosis (OMIM, 230000) is a rare autosomal recessive LSD caused by the deficiency of the α-L-fucosidase enzyme (EC 3.2.1.51) coded by FUCA1 gene, that causes accumulation of glycopeptides such as fucosyl-glycopeptides and oligosaccharides in some tissues [150]. In Colombia, a study of Valero-Rubio et al [150] analyzed in keratinocytes the effect of FUCA1 gene knock-down to understand the pathogenesis in skin lesions that fucosidosis patients present. The authors found that 387 genes were deregulated among cells transfected with a siRNA-A targeting FUCA1 (222 upregulated and 165 downregulated).…”

Section: Fucosidosismentioning

confidence: 99%

A perspective on research, diagnosis, and management of lysosomal storage disorders in Colombia

Puentes-Tellez

Lerma-Barbosa

Garzón-Jaramillo

et al. 2020

Heliyon

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Lysosomal storage diseases (LSDs) are a group of about 50 inborn errors of metabolism characterized by the lysosomal accumulation of partially or non-degraded molecules due to mutations in proteins involved in the degradation of macromolecules, transport, lysosomal biogenesis or modulators of lysosomal environment. Significant advances have been achieved in the diagnosis, management, and treatment of LSDs patients. In terms of approved therapies, these include enzyme replacement therapy (ERT), substrate reduction therapy, hematopoietic stem cell transplantation, and pharmacological chaperone therapy. In this review, we summarize the Colombian experience in LSDs thorough the evidence published. We identified 113 articles published between 1995 and 2019 that included Colombian researchers or physicians, and which were mainly focused in Mucopolysaccharidoses, Pompe disease, Gaucher disease, Fabry disease, and Tay-Sachs and Sandhoff diseases. Most of these articles focused on basic research, clinical cases, and mutation reports. Noteworthy, implementation of the enzyme assay in dried blood samples, led to a 5-fold increase in the identification of LSD patients, suggesting that these disorders still remain undiagnosed in the country. We consider that the information presented in this review will contribute to the knowledge of a broad spectrum of LSDs in Colombia and will also contribute to the development of public policies and the identification of research opportunities.

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Transcriptomic analysis of FUCA1 knock‐down in keratinocytes reveals new insights into the pathogenesis of fucosidosis skin lesions

Cited by 7 publications

References 41 publications

Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis

Saliva proteomic patterns in patients with molar incisor hypomineralization

A perspective on research, diagnosis, and management of lysosomal storage disorders in Colombia

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