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Status |
Public on Dec 01, 2016 |
Title |
Decreases in 15-lipoxigenase metabolites in Olmsted syndrome model rats |
Organism |
Rattus norvegicus |
Experiment type |
Expression profiling by array
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Summary |
Olmsted syndrome (OS) is a congenital dermatosis characterized by palmoplantar keratoderma and periorificial keratotic plaque. TRPV3 (transient receptor potential vanilloid subtype 3) is the causative gene of OS and encodes a thermosensitive Ca2+-channel. However, the molecular mechanism causing the pathological development of OS is unclear. We aimed to reveal the molecular mechanism underlying the OS pathology from the perspective of lipid metabolism. Comprehensive lipidomics as well as microarray analyses were conducted on samples from non-lesional skin area of an OS rat model (Ht rats). Infiltration of mast cells, eosinophils, and neutrophils and an increase in fibrotic region were detected in unaffected skin area of Ht rats. Among ~600 lipid species examined, levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides were decreased by ≥16-fold in Ht rats compared to wild type rats. Consistent with the decreases in the 15-LOX metabolites, expression levels of the 15-LOXs, Alox15 and Alox15b, were largely reduced. On the other hand, expression levels of the cytokines/chemokines Il36b, Ccl20, Cxcl1, and Cxcl2 and those of the Ca2+-binding proteins S100a8 and S100a9, which are implicated in epidermal proliferation, were increased. The pro-inflammatory state of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS.
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Overall design |
Effect of TRPV3 gain of function mutation on non-lesioned dorsal skin tissue from pool samples of n = 3 wild-type and of n=3 Ht rats. Biological replicates: a replicate for 25-wk wild-type and 25-wk Ht.
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Contributor(s) |
Wakabayashi M, Yoshioka T |
Citation(s) |
28024685 |
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Submission date |
Jul 12, 2016 |
Last update date |
Mar 02, 2017 |
Contact name |
Masato Wakabayashi |
E-mail(s) |
masato.wakabayashi@shionogi.co.jp
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Organization name |
Shionogi & Co., Ltd.
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Street address |
3-1-1, Futaba-cho
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City |
Toyonaka-shi |
State/province |
Osaka |
ZIP/Postal code |
561-0825 |
Country |
Japan |
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Platforms (1) |
GPL22145 |
Agilent-074036 SurePrint G3 Rat GE v2 8x60K Microarray G4858A (Feature Number version) |
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Samples (2) |
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Relations |
BioProject |
PRJNA328604 |
Supplementary file |
Size |
Download |
File type/resource |
GSE84294_RAW.tar |
16.5 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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