Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure
Abstract Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure (HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II...
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Sociedade Brasileira de Genética
2023-03-01
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Series: | Genetics and Molecular Biology |
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Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572023000100101&lng=en&tlng=en |
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author | Yu Ren Yun Wu Wenshuai He Yingjie Tian Xingsheng Zhao |
author_facet | Yu Ren Yun Wu Wenshuai He Yingjie Tian Xingsheng Zhao |
author_sort | Yu Ren |
collection | DOAJ |
description | Abstract Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure (HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II (Ang II) treatment. Isolated MSCs-exosomes were identified by transmission electron microscope and CD63 detection. Apoptosis rate was measured by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Levels of inflammatory factors [interleukin (IL)-1β, IL-4, IL-6, and tumor necrosis factor (TNF)-α] and brain natriuretic peptide (BNP) were determined by ELISA. Expression of apoptosis-related proteins [Bax, B-cell lymphoma-2 (Bcl-2), and caspase 3] and Hippo-Yes-associated protein (YAP) pathway-related proteins [YAP, phosphor (p)-YAP, and tafazzin (TAZ)] was detected by western blotting. Cardiomyocyte hypertrophy of H9c2 cells induced by Ang II was ameliorated by MSCs-exosomes treatment. MSCs-exosomes downregulated Bax and caspase 3 levels and upregulated Bcl-2 level in Ang II-induced H9c2 cells. MSCs-exosomes also reduced the levels of BNP, IL-1β, IL-4, IL-6, and TNF-α in Ang II-induced H9c2 cells. Meanwhile, p-YAP was downregulated and TAZ was upregulated after MSCs-exosomes administration. In conclusion, MSCs-exosomes alleviate the apoptosis and inflammatory response of cardiomyocyte via deactivating Hippo-YAP pathway in HF. |
first_indexed | 2024-04-10T00:40:05Z |
format | Article |
id | doaj.art-dd75786010804fadadccba1803085737 |
institution | Directory Open Access Journal |
issn | 1678-4685 |
language | English |
last_indexed | 2024-04-10T00:40:05Z |
publishDate | 2023-03-01 |
publisher | Sociedade Brasileira de Genética |
record_format | Article |
series | Genetics and Molecular Biology |
spelling | doaj.art-dd75786010804fadadccba18030857372023-03-14T07:31:53ZengSociedade Brasileira de GenéticaGenetics and Molecular Biology1678-46852023-03-0146110.1590/1678-4685-gmb-2022-0221Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failureYu RenYun WuWenshuai HeYingjie TianXingsheng Zhaohttps://orcid.org/0000-0002-1346-6913Abstract Mesenchymal stem cells-derived exosomes (MSCs-exosomes) reportedly possess cardioprotective effects. This study investigated the therapeutic potential and mechanisms of MSCs-exosomes on heart failure (HF). H9c2 cells were used to establish a cardiomyocyte hypertrophy model by angiotensin II (Ang II) treatment. Isolated MSCs-exosomes were identified by transmission electron microscope and CD63 detection. Apoptosis rate was measured by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Levels of inflammatory factors [interleukin (IL)-1β, IL-4, IL-6, and tumor necrosis factor (TNF)-α] and brain natriuretic peptide (BNP) were determined by ELISA. Expression of apoptosis-related proteins [Bax, B-cell lymphoma-2 (Bcl-2), and caspase 3] and Hippo-Yes-associated protein (YAP) pathway-related proteins [YAP, phosphor (p)-YAP, and tafazzin (TAZ)] was detected by western blotting. Cardiomyocyte hypertrophy of H9c2 cells induced by Ang II was ameliorated by MSCs-exosomes treatment. MSCs-exosomes downregulated Bax and caspase 3 levels and upregulated Bcl-2 level in Ang II-induced H9c2 cells. MSCs-exosomes also reduced the levels of BNP, IL-1β, IL-4, IL-6, and TNF-α in Ang II-induced H9c2 cells. Meanwhile, p-YAP was downregulated and TAZ was upregulated after MSCs-exosomes administration. In conclusion, MSCs-exosomes alleviate the apoptosis and inflammatory response of cardiomyocyte via deactivating Hippo-YAP pathway in HF.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572023000100101&lng=en&tlng=enMesenchymal stem cellsexosomescardiomyocyte hypertrophyheart failureHippo-YAP pathway |
spellingShingle | Yu Ren Yun Wu Wenshuai He Yingjie Tian Xingsheng Zhao Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure Genetics and Molecular Biology Mesenchymal stem cells exosomes cardiomyocyte hypertrophy heart failure Hippo-YAP pathway |
title | Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure |
title_full | Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure |
title_fullStr | Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure |
title_full_unstemmed | Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure |
title_short | Exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through Hippo-YAP pathway in heart failure |
title_sort | exosomes secreted from bone marrow mesenchymal stem cells suppress cardiomyocyte hypertrophy through hippo yap pathway in heart failure |
topic | Mesenchymal stem cells exosomes cardiomyocyte hypertrophy heart failure Hippo-YAP pathway |
url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572023000100101&lng=en&tlng=en |
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