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| Status |
Public on Nov 30, 2018 |
| Title |
Patients with Congenital Ichthyosis and TGM1 Mutations Overexpress Other ARCI Genes in the Skin: Part of a Barrier Repair Response? |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of monogenic skin disorders caused by mutations in any of >10 different genes, many of which are involved in epidermal synthesis of ω-O-acylceramides (acylCer), an essential precursor of the corneocyte lipid envelope that is also dependent on transglutaminase-1 for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations, the most common cause of ARCI, might lead to a compensatory overexpression of transcripts involved in barrier repair, including ARCI-causing genes. Using microarray we examined the global mRNA expression profile in skin biopsies from five ARCI-patients with TGM1 mutations and four healthy controls. There were a total of 602 differentially expressed genes (adjusted P<0.05). Gene ontology analysis showed enrichment of mRNA encoding proteins associated with biological pathways mainly involved in keratinocyte differentiation and adaptive/innate immune response. Moreover, among non-syndromic ARCI-causing genes, seven out of twelve were significantly increased (log2fold -change=0.98-2.05). Four genes causing syndromic ichthyosis and seven other genes involved in biosynthesis of fatty acyl-CoA and ceramides were also significantly affected. This study reveals upregulation of several ichthyosis-causing genes in the skin of patients with TGM1 mutations, indicating a compensatory induction of acylCer biosynthesis as a part of a barrier repair mechanism.
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| Overall design |
Skin biopsies were obtained at the buttocks of ichthyosis patients with TGM1 mutations (n=5) and healthy controls (n=4).
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| Contributor(s) |
Zhang H, Ericsson M, Weström S, Vahlquist A, Virtanen M, Törmä H |
| Citation(s) |
30372788 |
| |
| Submission date |
Nov 29, 2017 |
| Last update date |
Mar 01, 2019 |
| Contact name |
Hans Törmä |
| E-mail(s) |
[email protected]
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| Organization name |
Uppsala University
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| Department |
Dept of Medical Sciences
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| Lab |
Rudbeck Laboratory/Dermatology
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| Street address |
Dag Hammarskjölds väg 20
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| City |
Uppsala |
| ZIP/Postal code |
75185 |
| Country |
Sweden |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA420190 |
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