Shared gene expression patterns in mesenchymal progenitors derived from lung and epidermis in pulmonary arterial hypertension: identifying key pathways in pulmonary vascular disease.

Autor: Gaskill C; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Marriott S; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Pratap S; Meharry Medical College, Nashville, Tennessee, USA., Menon S; Pulmonary Vascular Research Institute, Kochi; and AnalyzeDat Consulting Services, Kerala, India., Hedges LK; Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA., Fessel JP; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Kropski JA; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Ames D; Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA., Wheeler L; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Loyd JE; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Hemnes AR; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA., Roop DR; Department of Dermatology; and Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado, Aurora, Colorado, USA., Klemm DJ; Division of Pulmonary and Critical Care Medicine, Department of Medicine; and Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado, Aurora, Colorado, USA., Austin ED; Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA., Majka SM; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, Tennessee, USA.
Jazyk: angličtina
Zdroj: Pulmonary circulation [Pulm Circ] 2016 Dec; Vol. 6 (4), pp. 483-497.
DOI: 10.1086/688314
Abstrakt: Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant-derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction. By analyzing the genetic signatures and pathways associated with abnormal ABCG2 lung MPC phenotypes during PAH and evaluating them in lung- and skin-derived MCs, we have identified potential predictor genes for detection of PAH as well as a targetable mechanism to restore MPCs and microvascular function. These studies are the first to explore the utility of expanding the study of ABCG2 MPC regulation of the pulmonary microvasculature to the epidermis, in order to identify potential markers for adult lung vascular disease, such as PAH.
Databáze: MEDLINE
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