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| Status |
Public on Dec 10, 2010 |
| Title |
Gene expression changes in NFAT5/TonEBP under isotonic and hypertonic conditions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
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| Overall design |
Quadruplicate samples were collected for each condition and then pooled into a single sample for hybridization to microarrays.
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| Contributor(s) |
Lamitina ST, Lee SD, Choi SY, Lim SW, Ho SN, Go WY, Kwon HM |
| Citation(s) |
21209002 |
| Submission date |
Dec 02, 2010 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Todd Lamitina |
| E-mail(s) |
lamitina@mail.med.upenn.edu
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| Phone |
215-898-3223
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| Organization name |
University of Pennsylvania
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| Department |
Physiology
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| Street address |
3700 Hamilton Walk, A702
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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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 (4)
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| GSM634287 |
Wild type MEF cells, isotonic conditions |
| GSM634288 |
Wild type MEF cells, hypertonic conditions |
| GSM634289 |
NFAT5/TonEBP KO MEF cells, isotonic conditions |
| GSM634290 |
NFAT5/TonEBP KO MEF cells, hypertonic conditions |
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| Relations |
| BioProject |
PRJNA135623 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE25816_RAW.tar |
16.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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