Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension
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 inhibitor...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/840737 |
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| author | Bo Zhang Min Shen Min Xu Li-Li Liu Ying Luo Dun-Quan Xu Yan-Xia Wang Man-Ling Liu Yi Liu Hai-Ying Dong Peng-Tao Zhao Zhi-Chao Li |
| author_facet | Bo Zhang Min Shen Min Xu Li-Li Liu Ying Luo Dun-Quan Xu Yan-Xia Wang Man-Ling Liu Yi Liu Hai-Ying Dong Peng-Tao Zhao Zhi-Chao Li |
| author_sort | Bo Zhang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b218147ddb2f41d2812554b82e514bfc |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-b218147ddb2f41d2812554b82e514bfc2025-08-20T02:23:19ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/840737840737Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary HypertensionBo Zhang0Min Shen1Min Xu2Li-Li Liu3Ying Luo4Dun-Quan Xu5Yan-Xia Wang6Man-Ling Liu7Yi Liu8Hai-Ying Dong9Peng-Tao Zhao10Zhi-Chao Li11Department of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaDepartment of Pathology, Xijing Hospital, Fourth Military Medical University, Changle West Road 169, Xi'an 710032, ChinaPulmonary 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.http://dx.doi.org/10.1155/2012/840737 |
| spellingShingle | Bo Zhang Min Shen Min Xu Li-Li Liu Ying Luo Dun-Quan Xu Yan-Xia Wang Man-Ling Liu Yi Liu Hai-Ying Dong Peng-Tao Zhao Zhi-Chao Li Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension Mediators of Inflammation |
| title | Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension |
| title_full | Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension |
| title_fullStr | Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension |
| title_full_unstemmed | Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension |
| title_short | Role of Macrophage Migration Inhibitory Factor in the Proliferation of Smooth Muscle Cell in Pulmonary Hypertension |
| title_sort | role of macrophage migration inhibitory factor in the proliferation of smooth muscle cell in pulmonary hypertension |
| url | http://dx.doi.org/10.1155/2012/840737 |
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