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| Status |
Public on Jan 01, 2016 |
| Title |
Regulation of ER Homeostasis and Cell Cycle by Pax4 Enhances β-Cell Survival and Protects Mice Against Experimental Autoimmune Diabetes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Strategies to enhance islet b-cell survival and regeneration while refraining inflammation through manipulation of molecular targets would provide means to stably replenish the deteriorating functional b-cell mass detected in both Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM). Herein we report that over expression of the islet enriched transcription factor Pax4 refrains development of hyperglycemia in the RIP-B7.1 mouse model of T1DM through reduced insulitis, decreased b-cell apoptosis correlating with diminished DNA damage and increased proliferation. Transcriptomics revealed up regulation of genes involved in immunomodulation, cell cycle and ER homeostasis in islets over expressing Pax4 as compared to the T2DM-linked mutant variant Pax4R129W. Pax4 but not Pax4R129W protected islets from thapsigargin-mediated ER-stress apoptosis. Collectively, Pax4 is a critical signaling hub coordinating regulation of distinct molecular pathways resulting in improved b-cell fitness whereas Pax4R129W sensitizes to death under stress. More importantly we highlight potential common pharmacological targets for the treatment of DM.
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| Overall design |
4 groups of 3 samples each. Primary isolated islets of langerhans from either Pax4/rtTA or Pax4R121W/rtTA mice treated or not with Doxicycline.
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| Contributor(s) |
Alvarez-Mercado AI, Gil JM, Jiménez-Moreno CM, Martin-Montalvo A, Cobo-Vuilleumier N, Lorenzo PI, de Gracia Herrera Gómez I, Noriega LL, Pérez-Florido J, Santoyo-López J, Meda P, Spyrantis A, Boehm BO, Gauthier BR |
| Citation(s) |
26813254 |
| |
| Submission date |
Oct 30, 2014 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Benoit Raymond Gauthier |
| E-mail(s) |
benoit.gauthier@cabimer.es
|
| Organization name |
Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER)
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| Department |
Stem Cells
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| Lab |
Pancreatic Islet Development and Regeneration Unit
|
| Street address |
Americo Vespucio Avenue
|
| City |
Seville |
| State/province |
Seville |
| ZIP/Postal code |
41092 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA265835 |
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