Expression data from pulmonary arterial endothelial cells treated with siRNA control or siGLS in stiff or soft matrix
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ABSTRACT: 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 r
ORGANISM(S): Homo sapiens
SUBMITTER: Thomas BERTERO
PROVIDER: E-GEOD-75793 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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