James Loyd
Faculty Member
Last active: 2/12/2015

Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension.

West JD, Austin ED, Gaskill C, Marriott S, Baskir R, Bilousova G, Jean JC, Hemnes AR, Menon S, Bloodworth NC, Fessel JP, Kropski JA, Irwin D, Ware LB, Wheeler L, Hong CC, Meyrick B, Loyd JE, Bowman AB, Ess KC, Klemm DJ, Young PP, Merryman WD, Kotton D, Majka SM
Am J Physiol Cell Physiol. 2014 307 (5): C415-30

PMID: 24871858 · PMCID: PMC4154073 · DOI:10.1152/ajpcell.00057.2014

Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis for disease. Previous studies on patient samples were limited by end-stage disease effects or by use of nonadherent cells, which are not ideal to model vascular cells in vivo. These studies addressed the hypothesis that pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments were initially conducted to analyze cell types at different stages of vascular differentiation (mesenchymal stromal and endothelial) derived from PAH patient-specific induced pluripotent stem (iPS) cells. Molecular pathways that were altered in the PAH cell lines were then compared with those in fibroblasts from 21 patients, including those with idiopathic and heritable PAH. Wnt was identified as a target pathway and was validated in vitro using primary patient mesenchymal and endothelial cells. Taken together, our data suggest that the molecular lesions that cause PAH are present in all cell types evaluated, regardless of origin, and that stimulation of the Wnt signaling pathway was a common molecular defect in both heritable and idiopathic PAH.

MeSH Terms (10)

Cell Differentiation Cell Line Cells, Cultured Endothelial Cells Familial Primary Pulmonary Hypertension Humans Hypertension, Pulmonary Pluripotent Stem Cells Respiratory Mucosa Wnt Signaling Pathway

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