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https://doi.org/10.1371/journal.pbio.3000941
Title: | YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction | Authors: | Mia, Masum M Cibi, Dasan Mary Abdul Ghani, Siti Aishah Binte Song, Weihua Tee, Nicole Ghosh, Sujoy Mao, Junhao Olson, Eric N Singh, Manvendra K |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Biology Life Sciences & Biomedicine - Other Topics ALTERNATIVELY ACTIVATED MACROPHAGES SET ENRICHMENT ANALYSIS HISTONE DEACETYLASE 3 HIPPO PATHWAY YAP POLARIZATION TRANSCRIPTION INHIBITION EXPRESSION REPAIR |
Issue Date: | 1-Dec-2020 | Publisher: | PUBLIC LIBRARY SCIENCE | Citation: | Mia, Masum M, Cibi, Dasan Mary, Abdul Ghani, Siti Aishah Binte, Song, Weihua, Tee, Nicole, Ghosh, Sujoy, Mao, Junhao, Olson, Eric N, Singh, Manvendra K (2020-12-01). YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction. PLOS BIOLOGY 18 (12). ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pbio.3000941 | Abstract: | Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI. | Source Title: | PLOS BIOLOGY | URI: | https://scholarbank.nus.edu.sg/handle/10635/201109 | ISSN: | 15449173 15457885 |
DOI: | 10.1371/journal.pbio.3000941 |
Appears in Collections: | Elements Staff Publications |
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