The Hepcidin / Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells

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Title: The Hepcidin / Ferroportin axis modulates proliferation of pulmonary artery smooth muscle cells
Authors: Ramakrishnan, L
Pedersen, SL
Toe, QK
West, LE
Mumby, S
Casbolt, H
Garfield, B
Issitt, T
Lawrie, A
Wort, SJ
Quinlan, GJ
Item Type: Journal Article
Abstract: Studies were undertaken to examine any role for the hepcidin/ferroportin axis in proliferative responses of human pulmonary artery smooth muscle cells (hPASMCs). Entirely novel findings have demonstrated the presence of ferroportin in hPASMCs. Hepcidin treatment caused increased proliferation of these cells most likely by binding ferroportin resulting in internalisation and cellular iron retention. Cellular iron content increased with hepcidin treatment. Stabilisation of ferroportin expression and activity via intervention with the therapeutic monoclonal antibody LY2928057 reversed proliferation and cellular iron accumulation. Additionally, IL-6 treatment was found to enhance proliferation and iron accumulation in hPASMCs; intervention with LY2928057 prevented this response. IL-6 was also found to increase hepcidin transcription and release from hPASMCs suggesting a potential autocrine response. Hepcidin or IL-6 mediated iron accumulation contributes to proliferation in hPASMCs; ferroportin mediated cellular iron excretion limits proliferation. Haemoglobin also caused proliferation of hPASMCs; in other novel findings, CD163, the haemoglobin/haptoglobin receptor, was found on these cells and offers a means for cellular uptake of iron via haemoglobin. Il-6 was also found to modulate CD163 on these cells. These data contribute to a better understanding of how disrupted iron homeostasis may induce vascular remodelling, such as in pulmonary arterial hypertension.
Issue Date: 28-Aug-2018
Date of Acceptance: 10-Aug-2018
URI: http://hdl.handle.net/10044/1/63407
DOI: http://do.doi.org/10.1038/s41598-018-31095-0
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre- ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per- mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: British Heart Foundation
Funder's Grant Number: PG/15/56/31573
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
IRON-DEFICIENCY
HYPERTENSION
HEPCIDIN
GROWTH
HOMEOSTASIS
DISRUPTION
RESISTANCE
HEMOLYSIS
THERAPY
DISEASE
Article Number: 12972
Appears in Collections:Division of Surgery
National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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