Objective: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated.
Approach And Results: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1/ApoE) mice and found that atherosclerosis was greater in MED1/ApoE mice than in MED1/ApoE littermates. The gene expression of M1 markers was increased and that of M2 markers decreased in both aortic wall and peritoneal macrophages from MED1/ApoE mice, whereas MED1 overexpression rectified the changes in M1/M2 expression. Moreover, LDLR (low-density lipoprotein receptor)-deficient mice received bone marrow from MED1 mice showed greater atherosclerosis. Mechanistically, MED1 ablation decreased the binding of PPARγ (peroxisome proliferator-activated receptor γ) and enrichment of H3K4me1 and H3K27ac to upstream region of M2 marker genes. Furthermore, interleukin 4 induction of PPARγ and MED1 increased the binding of PPARγ or MED1 to the PPAR response elements of M2 marker genes.
Conclusions: Our data suggest that MED1 is required for the PPARγ-mediated M2 phenotype switch, with M2 marker genes induced but M1 marker genes suppressed. MED1 in macrophages has an antiatherosclerotic role via PPARγ-regulated transactivation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739054 | PMC |
| http://dx.doi.org/10.1161/ATVBAHA.117.309672 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HOXA5 induces M2 macrophage polarization to attenuate carotid atherosclerosis by activating MED1.
IUBMB Life
September 2021
Department of Vascular Surgery, The First Hospital of China Medical University, Shenyang, China.
Macrophage polarization is of great importance in the formation of atherosclerotic plaque. Homeobox A5 (HOXA5), one of the homeobox transcription factors, has been revealed to be closely associated with macrophage phenotype switching. This study aims to investigate the role of HOXA5 in carotid atherosclerosis (CAS).
View Article and Find Full Text PDFMediator 1 Is Atherosclerosis Protective by Regulating Macrophage Polarization.
Arterioscler Thromb Vasc Biol
August 2017
From the Research Institute of Atherosclerotic Disease, Health Science Center and Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China (L.B., Q.L., H.G., S.Z., R.L., R.W., E.L.), Laboratory Animal Center, Health Science Center (L.B., Q.L., H.G., S.Z., R.L., R.W., E.L.), Cardiovascular Research Center, School of Basic Medical Sciences, Health Science Center (L.B., Z.L., J.Z., N.W., J.Y.-J.S.), Xi'an Jiaotong University, Shaanxi, China; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL (Y.J., J.K.R.); Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Japan (J.F.); and Division of Cardiology, Department of Medicine, University of California, San Diego, La Jolla (J.Y.-J.S.).
Objective: MED1 (mediator 1) interacts with transcription factors to regulate transcriptional machinery. The role of MED1 in macrophage biology and the relevant disease state remains to be investigated.
Approach And Results: To study the molecular mechanism by which MED1 regulates the M1/M2 phenotype switch of macrophage and the effect on atherosclerosis, we generated MED1/apolipoprotein E (ApoE) double-deficient (MED1/ApoE) mice and found that atherosclerosis was greater in MED1/ApoE mice than in MED1/ApoE littermates.
Apolipoprotein E as a target for developing new therapeutics for Alzheimer's disease based on studies from protein, RNA, and regulatory region of the gene.
J Mol Neurosci
August 2004
Department of Psychiatry and of Medical and Molecular Genetics, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Alzheimer's disease (AD), the most common form of dementia, is a progressive, degenerative disorder of the central nervous system. The major hallmarks of AD include selective neuronal cell death and the presence of amyloid deposits and neurofibrillary tangles. Apolipoprotein E (ApoE) has also been shown to colocalize with these neuropathological lesions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!