Type

Journal Article

Authors

Paul McLoughlin
Sean Gaine
Michael P Keane
John A Belperio
Michelle Sands
Katherine Howell
Brian McCullagh
Christine M Costello

Subjects

Biochemistry

Topics
chemistry female anoxia metabolism male idiopathic pulmonary fibrosis blood chemokine cxcl12 microvessels middle aged cxcr7 protein human mice inbred c57bl physiology hypertension pulmonary rats animals mice cells cultured rats sprague dawley cxcl12 protein human wound healing adult lung humans receptors cxcr4 receptors cxcr vascular diseases

A role for the CXCL12 receptor, CXCR7, in the pathogenesis of human pulmonary vascular disease. (2011)

Abstract Given the critical role that endothelial cell dysfunction plays in the pathogenesis of pulmonary hypertensive diseases, we set out to establish if CXCR7, a receptor for the pro-angiogenic ligand CXCL12, is expressed in the vasculature of human lung diseases and examine its role in mediating CXCL12-induced responses in primary pulmonary human microvascular endothelial cells. Receptor and ligand expression was examined in control and explanted human hypertensive lungs, in human plasma and in hypoxic rodent lungs, by ELISA and immunohistochemical studies. Functional in vitro experiments examined the role of CXCR7 in CXCL12-induced lung microvascular endothelial cell proliferation, migration, and wound regeneration and repair. CXCR7 is elevated in the endothelium of explanted human hypertensive lungs and circulating CXCL12 concentrations are significantly elevated in disease. We demonstrate that alveolar hypoxia similar to that found in lung disease increases CXCR7 expression in the pulmonary endothelium. Furthermore, CXCR7 is the receptor through which endothelial cell regeneration and repair, and proliferation, is mediated, whereas signalling via CXCR4 is essential for chemotactic cell migration. Our findings demonstrate that CXCR7 has a critical but previously unrecognised role to play in endothelial cell proliferation, suggesting that CXCR7-mediated signalling may be functionally important in pulmonary vascular diseases.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Paul McLoughlin, Sean Gaine, Michael P Keane, John A Belperio, Michelle Sands, Katherine Howell, Brian McCullagh, Christine M Costello

Experts in our system

1
Paul McLoughlin
University College Dublin
 
2
Sean Gaine
University College Dublin
Total Publications: 9
 
3
Michael P Keane
University College Dublin
Total Publications: 23
 
4
Brian N. McCullagh
University College Dublin
Total Publications: 6