ArticleMolecular medicine (Cambridge, Mass.)2012
Macrophage migration inhibitory factor mediates hypoxia-induced pulmonary hypertension.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 73 citations in OpenAlex.
- Trial
- Combined single-cell transcriptome and Mendelian randomization to identify and validate prognostic genes associated with endoplasmic reticulum stress and butyrate metabolism in lung adenocarcinoma.Frontiers in genetics · 2026Article
- Integration of Single-Cell RNA Sequencing Data and Bulk Sequencing Data to Characterise the CD8+ T-Cell Exhaustion Mediated Immune Microenvironment in CRC.Journal of cellular and molecular medicine · 2025Article
- Elevated Macrophage Migration Inhibitory Factor 1 Is Associated with Left and Right Ventricular Systolic Dysfunction in Heart Failure with Reduced Ejection Fraction.Biomedicines · 2025Article
- A Mendelian randomization study on the association between systemic inflammatory regulators and essential and secondary hypertension.Frontiers in cardiovascular medicine · 2024Article
- Tensions in Taxonomies: Current Understanding and Future Directions in the Pathobiologic Basis and Treatment of Group 1 and Group 3 Pulmonary Hypertension.Comprehensive Physiology · 2023Review
- Inflammation and immunity in the pathogenesis of hypoxic pulmonary hypertension.Frontiers in immunology · 2023Review
- A narrative review of research advances in hypoxic pulmonary hypertension.Annals of translational medicine · 2022Review
- Cytokines, Chemokines, and Inflammation in Pulmonary Arterial Hypertension.Advances in experimental medicine and biology · 2021Article
- Article
- MIF inhibition enhances pulmonary angiogenesis and lung development in congenital diaphragmatic hernia.Pediatric research · 2019Article
- Macrophage Migration Inhibitory Factor (MIF) Inhibition in a Murine Model of Bleomycin-Induced Pulmonary Fibrosis.International journal of molecular sciences · 2018Article
- Macrophage migration inhibitory factor (MIF) in the development and progression of pulmonary arterial hypertension.Global cardiology science & practice · 2018Review
- Hypoxia induces pulmonary arterial fibroblast proliferation, migration, differentiation and vascular remodeling via the PI3K/Akt/p70S6K signaling pathway.International journal of molecular medicine · 2018Article
- Macrophage migration inhibitory factor as a novel biomarker of portopulmonary hypertension.Pulmonary circulation · 2016Article
- Spotlight on Inflammation in Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2015Article
- Deletion of STAT5a/b in vascular smooth muscle abrogates the male bias in hypoxic pulmonary hypertension in mice: implications in the human disease.Molecular medicine (Cambridge, Mass.) · 2015Article
- Macrophage migration inhibitory factor is a novel determinant of cigarette smoke-induced lung damage.American journal of respiratory cell and molecular biology · 2014Article
- Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension.Circulation research · 2014Review
- Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice.PloS one · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significantly higher than in the control group (P = 0.004 and 0.007, respectively). MIF involvement with hypoxia-induced fibroblast proliferation was examined in both a human cell-line and primary mouse cells from wild-type (mif⁺/⁺) and MIF-knockout (mif⁻/⁻) mice. In vitro, hypoxia-increased MIF mRNA, extracellular MIF protein accumulation and cell proliferation. Inhibition of MIF inflammatory activity reduced hypoxia-induced cell proliferation. However, hypoxia only increased proliferation of mif⁻/⁻ cells when they were supplemented with media from mif⁺/⁺ cells. This growth increase was suppressed by MIF inhibition. In vivo, chronic exposure of mice to a normobaric atmosphere of 10% oxygen increased lung tissue expression of mRNA encoding MIF and accumulation of MIF in plasma. Inhibition of the MIF inflammatory active site, during hypoxic exposure, significantly reduced pulmonary vascular remodeling, cardiac hypertrophy and right ventricular systolic pressure. The data suggest that MIF plays a critical role in hypoxia-induced PH, and its inhibition may be beneficial in preventing the development and progression of the disease.
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