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| Status |
Public on Sep 08, 2015 |
| Title |
AMPK epidermal inhibition promotes HuR cytoplasmic localization eliciting post-transcriptional inflammatory response in psoriasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
IL-20 cytokines are involved in the establishment of psoriasis, a common chronic skin inflammation epidemiologically associated with metabolic syndrome, but molecular mechanisms underlying their over-expression remain to be elucidated. We find that keratinocytes (KCs) expressed IL-20 and lymphocytes expressed IL-22 cytokines up-regulation occurs at post-transcriptional level with stabilization of their RNA messengers. Looking at psoriatic epidermis, we observe that the p38/MK2 pathway is not activated but that the RNA-binding protein (RBP) HuR re-localizes in keratinocytes cytoplasm, suggesting post-transcriptional regulation of numerous mRNAs. HuR ribonucleoprotein immunoprecipitations analyzed by high-throughput sequencing (RIP-Seq) identify potential pre-mature and mature RNA targets for uninvolved and involved skin and confirms that HuR activity is displaced from the nucleus to the cytoplasm. Numerous psoriasis up-regulated transcripts are HuR targets and HuR knockdown reduces expression of transcripts like beta-defensin-2, CXCL-10 or IL-2, suggesting an implication of HuR in pathophysiological processes such as morphological, immune and metabolic inflammatory responses. Finally, metabolic disorders affecting psoriatic keratinocytes are responsible for HuR cytoplasmic localization since a decreased activity of the cellular metabolic sensor AMPK, that is observed in human psoriatic epidermis, is sufficient to promote HuR cytosolic localization as well as IL-20 over-production both in human keratinocytes and in vivo in mouse epidermis where it then initiates psoriasis-like histological changes. These results may provide insights into molecular links between metabolism and post-transcriptional networks during chronic inflammation, as illustrated in psoriasis by mechanisms connecting AMPK, HuR and IL-20.
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| Overall design |
Analysis of HuR-binding RNA in uninvolved versus involved psoriatic samples by RIP-Seq. Samples from five different patients were used for both uninvolved and involved skin. RIP-Seq was also made using a control IgG.
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| Contributor(s) |
Garcin G, Guiraud I, Lacroix M, Genthon C, Rialle S, Joujoux JM, Meunier L, Lavabre-Bertrand T, Stoebner PE, Le Gallic L |
| Citation(s) |
26176762 |
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| Submission date |
Sep 04, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Geneviève Garcin |
| E-mail(s) |
genevieve.garcin@univ-montp2.fr
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| Organization name |
CNRS UMR5235
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| Lab |
DIMNP
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| Street address |
UM2. Place Eugene Bataillon. Bat 24.
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| City |
Montpellier |
| ZIP/Postal code |
34095 |
| Country |
France |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (3) |
| GSM1224487 |
IP HuR on involved psoriatic skin sample |
| GSM1224488 |
IP HuR on uninvolved psoriatic skin sample |
| GSM1224489 |
IP Ig on involved psoriatic skin sample |
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| Relations |
| BioProject |
PRJNA218050 |
| SRA |
SRP029588 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50598_Exonic.txt.gz |
35.2 Kb |
(ftp)(http) |
TXT |
| GSE50598_Intronic.txt.gz |
71.4 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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