title: Shared gene expression patterns in mesenchymal progenitors derived from lung and epidermis in pulmonary arterial hypertension: identifying key pathways in pulmonary vascular disease.
abstract: 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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Christa
authors.initials: C
authors.lastname: Gaskill
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Shennea
authors.initials: S
authors.lastname: Marriott
authors.affiliation: Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Sidd
authors.initials: S
authors.lastname: Pratap
authors.affiliation: Pulmonary Vascular Research Institute, Kochi; and AnalyzeDat Consulting Services, Kerala, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Menon
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Lora K
authors.initials: LK
authors.lastname: Hedges
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Fessel
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kropski
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: DeWayne
authors.initials: D
authors.lastname: Ames
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wheeler
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Hemnes
authors.affiliation: Department of Dermatology; and Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado, Aurora, Colorado, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Roop
authors.affiliation: 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.
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Klemm
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Austin
authors.affiliation: 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.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Majka
keywords: BMPR2; DKK1; LRP6; Wnt signaling; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; lung; mesenchymal progenitor cells; microvascular; pulmonary hypertension; skin