Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway
Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifuga...
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2020-12-01
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doaj-d3e1cf73fd5a47ba900c6837926842842020-12-05T04:20:50ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-0122948956Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP PathwayJie Ni0Yihai Liu1Kun Wang2Mingyue Wu3Lina Kang4Dujuan Sha5Biao Xu6Rong Gu7Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China; Department of General Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, P.R. ChinaDepartment of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. ChinaDepartment of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. ChinaDepartment of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. ChinaDepartment of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. ChinaDepartment of General Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, P.R. China; Corresponding author: Dujuan Sha, Department of General Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, P.R. China.Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China; Corresponding author: Biao Xu, Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China.Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China; Corresponding author: Rong Gu, Department of Cardiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 21008, P.R. China.Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. Utilizing the public Gene Expression Omnibus (GEO) database, we found that let-7i and Yes-associated protein 1 (YAP) could participate in the development of heart failure. In vitro, AC16 cardiomyocytes subjected to doxorubicin (DOX) were treated with TSC-exos or let-7i mimic. Flow cytometry showed that TSC-exos and let-7i both decreased cardiomyocyte apoptosis. In vivo, mice that were intraperitoneally injected into DOX received either PBS, TSC-exos, or AAV9-let7iup for let-7i overexpression. Mice receiving TSC-exos and AAV9-let7iup showed improved cardiac function and decreased inflammatory responses, accompanied by downregulated YAP signaling. Mechanistically, TSC-exos could transfer let-7i to cardiomyocytes and silence the YAP signaling pathway. In conclusion, TSC-exos could alleviate DOX-induced cardiac injury via the let-7i/YAP pathway, which sheds new light on the application of TSC-exos as a potential therapeutic tool for heart failure.http://www.sciencedirect.com/science/article/pii/S2162253120303267trophoblast stem cellsexosomeslet-7iYAPheart failure |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jie Ni Yihai Liu Kun Wang Mingyue Wu Lina Kang Dujuan Sha Biao Xu Rong Gu |
spellingShingle |
Jie Ni Yihai Liu Kun Wang Mingyue Wu Lina Kang Dujuan Sha Biao Xu Rong Gu Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway Molecular Therapy: Nucleic Acids trophoblast stem cells exosomes let-7i YAP heart failure |
author_facet |
Jie Ni Yihai Liu Kun Wang Mingyue Wu Lina Kang Dujuan Sha Biao Xu Rong Gu |
author_sort |
Jie Ni |
title |
Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway |
title_short |
Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway |
title_full |
Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway |
title_fullStr |
Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway |
title_full_unstemmed |
Trophoblast Stem-Cell-Derived Exosomes Improve Doxorubicin-Induced Dilated Cardiomyopathy by Modulating the let-7i/YAP Pathway |
title_sort |
trophoblast stem-cell-derived exosomes improve doxorubicin-induced dilated cardiomyopathy by modulating the let-7i/yap pathway |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2020-12-01 |
description |
Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. Utilizing the public Gene Expression Omnibus (GEO) database, we found that let-7i and Yes-associated protein 1 (YAP) could participate in the development of heart failure. In vitro, AC16 cardiomyocytes subjected to doxorubicin (DOX) were treated with TSC-exos or let-7i mimic. Flow cytometry showed that TSC-exos and let-7i both decreased cardiomyocyte apoptosis. In vivo, mice that were intraperitoneally injected into DOX received either PBS, TSC-exos, or AAV9-let7iup for let-7i overexpression. Mice receiving TSC-exos and AAV9-let7iup showed improved cardiac function and decreased inflammatory responses, accompanied by downregulated YAP signaling. Mechanistically, TSC-exos could transfer let-7i to cardiomyocytes and silence the YAP signaling pathway. In conclusion, TSC-exos could alleviate DOX-induced cardiac injury via the let-7i/YAP pathway, which sheds new light on the application of TSC-exos as a potential therapeutic tool for heart failure. |
topic |
trophoblast stem cells exosomes let-7i YAP heart failure |
url |
http://www.sciencedirect.com/science/article/pii/S2162253120303267 |
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