Open AccessShared Gene Expression Patterns in Mesenchymal Progenitors Derived from Lung and Epidermis in Pulmonary Arterial Hypertension: Identifying Key Pathways in Pulmonary Vascular Disease
Author(s) -
Gaskill Christa,
Marriott Shennea,
Pratap Sidd,
Me Swapna,
Hedges Lora K.,
Fessel Joshua P.,
Kropski Jonathan A.,
Ames DeWayne,
Wheeler Lisa,
Loyd James E.,
Hemnes Anna R.,
Roop Dennis R.,
Klemm Dwight J.,
Austin Eric D.,
Majka Susan M.
Publication year - 2016
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1086/688314
Subject(s) - medicine , mesenchymal stem cell , lung , pathology , progenitor cell , pulmonary hypertension , stem cell , microbiology and biotechnology , cardiology , biology
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.