title: Role of macrophage migration inhibitory factor in the proliferation of smooth muscle cell in pulmonary hypertension.
abstract: 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.
authors.affiliation: Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.forename: Dun-Quan
authors.initials: DQ
authors.lastname: Xu
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Man-Ling
authors.initials: ML
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Dong
authors.forename: Peng-Tao
authors.initials: PT
authors.lastname: Zhao
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*
chemical_list: D008263:Macrophage Migration-Inhibitory Factors