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| Status |
Public on Oct 21, 2019 |
| Title |
Expression data from 12 and 52 weeks old Rar-alpha WT and KO male mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Primary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. Inactivation of Rarα in mice led to major structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA.
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| Overall design |
Because Rar-alpha is a transcription factor, we performed transcriptome analysis to better understand the underlying molecular changes due to Rar-alpha invalidation and correlate them to the observed phenotype. Adrenal glands from 12 and 52 weeks old WT and Rar-alpha KO male mice were used. RNA was extracted from four adrenals per group and hybridized on Affymetrix microarray.
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| Contributor(s) |
El Zein RM, Zennaro M, Boulkroun S |
| Citation(s) |
31605007 |
| Submission date |
Sep 03, 2019 |
| Last update date |
Oct 21, 2019 |
| Contact name |
Franck Letourneur |
| E-mail(s) |
franck.letourneur@inserm.fr
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| Organization name |
INSERM
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| Department |
U1016
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| Lab |
genomic
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| Street address |
22 rue mechain
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| City |
Paris |
| ZIP/Postal code |
75014 |
| Country |
France |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (16)
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| GSM4058323 |
Adrenal_WT1_12weeks: 12 weeks old mice, Rar-alpha WT, biological rep1 |
| GSM4058324 |
Adrenal_WT2_12weeks: 12 weeks old mice, Rar-alpha WT, biological rep2 |
| GSM4058325 |
Adrenal_WT3_12weeks: 12 weeks old mice, Rar-alpha WT, biological rep3 |
| GSM4058326 |
Adrenal_WT4_12weeks: 12 weeks old mice, Rar-alpha WT, biological rep4 |
| GSM4058327 |
Adrenal_KO1_12weeks: 12 weeks old mice, Rar-alpha KO, biological rep1 |
| GSM4058328 |
Adrenal_KO2_12weeks: 12 weeks old mice, Rar-alpha KO, biological rep2 |
| GSM4058329 |
Adrenal_KO3_12weeks: 12 weeks old mice, Rar-alpha KO, biological rep3 |
| GSM4058330 |
Adrenal_KO4_12weeks: 12 weeks old mice, Rar-alpha KO, biological rep4 |
| GSM4058331 |
Adrenal_WT1_52weeks: 52 weeks old mice, Rar-alpha WT, biological rep1 |
| GSM4058332 |
Adrenal_WT2_52weeks: 52 weeks old mice, Rar-alpha WT, biological rep2 |
| GSM4058333 |
Adrenal_WT3_52weeks: 52 weeks old mice, Rar-alpha WT, biological rep3 |
| GSM4058334 |
Adrenal_WT4_52weeks: 52 weeks old mice, Rar-alpha WT, biological rep4 |
| GSM4058335 |
Adrenal_KO1_52weeks: 52 weeks old mice, Rar-alpha KO, biological rep1 |
| GSM4058336 |
Adrenal_KO2_52weeks: 52 weeks old mice, Rar-alpha KO, biological rep2 |
| GSM4058337 |
Adrenal_KO3_52weeks: 52 weeks old mice, Rar-alpha KO, biological rep3 |
| GSM4058338 |
Adrenal_KO4_52weeks: 52 weeks old mice, Rar-alpha KO, biological rep4 |
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| Relations |
| BioProject |
PRJNA563690 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136801_RAW.tar |
17.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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