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Mediators of Inflammation
Volume 2012 (2012), Article ID 840737, 10 pages
Research Article

Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension

1Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, China
2Department of Pathology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, China
3Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
4Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, China

Received 14 June 2011; Accepted 11 October 2011

Academic Editor: Dennis Daniel Taub

Copyright © 2012 Bo Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Pulmonary hypertension (PH) contributes to the mortality of patients with lung and heart diseases. However, the underlying mechanism has not been completely elucidated. Accumulating evidence suggests that inflammatory response may be involved in the pathogenesis of PH. Macrophage migration inhibitory factor (MIF) is a critical upstream inflammatory mediator which promotes a broad range of pathophysiological processes. The aim of the study was to investigate the role of MIF in the pulmonary vascular remodeling of hypoxia-induced PH. We found that MIF mRNA and protein expression was increased in the lung tissues from hypoxic pulmonary hypertensive rats. Intensive immunoreactivity for MIF was observed in smooth muscle cells of large pulmonary arteries (PAs), endothelial cells of small PAs, and inflammatory cells of hypoxic lungs. MIF participated in the hypoxia-induced PASMCs proliferation, and it could directly stimulate proliferation of these cells. MIF-induced enhanced growth of PASMCs was attenuated by MEK and JNK inhibitor. Besides, MIF antagonist ISO-1 suppressed the ERK1/2 and JNK phosphorylation induced by MIF. In conclusion, the current finding suggested that MIF may act on the proliferation of PASMCs through the activation of the ERK1/2 and JNK pathways, which contributes to hypoxic pulmonary hypertension.