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| Status |
Public on Sep 01, 2016 |
| Title |
Expression data from pulmonary arterial endothelial cells treated with siRNA control or siGLS in stiff or soft matrix |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Dysregulation of vascular stiffness and cellular metabolism occur early in pulmonary hypertension (PH). Yet, the mechanisms by which biophysical properties of extracellular matrix relate to metabolic processes and downstream PH phenotypes remain undefined. In cultured endothelial and smooth muscle cells and confirmed in PH-diseased human samples, we found that ECM stiffening activates the mechanosensitive factors YAP/TAZ to increase glycolysis and induce glutaminase (GLS) expression and glutaminolysis. Glutaminolysis replenishes aspartate for anabolic biosynthesis, thus sustaining proliferation and migration within stiff ECM. In vitro GLS inhibition blocks aspartate production, consequently reprogramming entire cellular proliferative pathways, while aspartate restores proliferation. In a rat model in vivo, GLS inhibition prevents hemodynamic and histologic manifestations of PH. Thus, mechanical ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis – a paradigm that advances our understanding of the connections of mechanical stimuli with dysregulated vascular metabolism and identifies new metabolic drug targets in PH.
We used microarrays to decipher the global program of gene expression involved in response to matrix stiffening and determined the implication of glutaminolysis (GLS) in these process
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| Overall design |
PAECs were transfected with an siRNA control (siNC) or a siRNA against GLS (siGLS) and cultivated on soft hydrogel (1kPa) or stiff hydrogel (50kPa). After 48h of transfection cells were lysate and RNA extract for hybridization on Affymetrix microarrays.
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| Contributor(s) |
Bertero T, Chan SY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Dec 08, 2015 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Thomas BERTERO |
| E-mail(s) |
thomas.bertero@unice.fr
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| Phone |
+ 33 (0)4 93 37 77 53
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| Organization name |
IRCAN, Nice CNRS UMR 7284 - INSERM U1081 - UNS
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| Department |
Medical School
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| Street address |
28 Av de Valombrose
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| City |
Nice |
| ZIP/Postal code |
06107 Cedex 02 |
| Country |
France |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| GSM1967875 |
siNC on soft matrix, biological replicate 1 |
| GSM1967876 |
siGLS on soft matrix, biological replicate 1 |
| GSM1967877 |
siNC on stiff matrix, biological replicate 1 |
| GSM1967878 |
siGLS on stiff matrix, biological replicate 1 |
| GSM1967879 |
siNC on soft matrix, biological replicate 2 |
| GSM1967880 |
siGLS on soft matrix, biological replicate 2 |
| GSM1967881 |
siNC on stiff matrix, biological replicate 2 |
| GSM1967882 |
siGLS on stiff matrix, biological replicate 2 |
| GSM1967883 |
siNC on soft matrix, biological replicate 3 |
| GSM1967884 |
siGLS on soft matrix, biological replicate 3 |
| GSM1967885 |
siNC on stiff matrix, biological replicate 3 |
| GSM1967886 |
siGLS on stiff matrix, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA305362 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE75793_RAW.tar |
92.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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