https://scholars.lib.ntu.edu.tw/handle/123456789/551958
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Tzu-Lin | en_US |
dc.contributor.author | Lai, Tsai-Chun | en_US |
dc.contributor.author | Lin, Shu-Rung | en_US |
dc.contributor.author | SHU-WHA LIN | en_US |
dc.contributor.author | Chen, Yu-Chen | en_US |
dc.contributor.author | Pu, Chi-Ming | en_US |
dc.contributor.author | Lee, I-Ta | en_US |
dc.contributor.author | JAW-SHIUN TSAI | en_US |
dc.contributor.author | Lee, Chiang-Wen | en_US |
dc.contributor.author | YUH-LIEN CHEN | en_US |
dc.date.accessioned | 2021-03-11T08:08:36Z | - |
dc.date.available | 2021-03-11T08:08:36Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/551958 | - |
dc.description.abstract | Rationale: Cardiovascular diseases, such as myocardial infarction (MI), are the leading causes of death worldwide. Reperfusion therapy is the common standard treatment for MI. However, myocardial ischemia/reperfusion (I/R) causes cardiomyocyte injury, including apoptosis and fibrosis. We aimed to investigate the effects of conditioned medium from adipose-derived stem cells (ADSC-CM) on apoptosis and fibrosis in I/R-treated hearts and hypoxia/reoxygenation (H/R)-treated cardiomyocytes and the underlying mechanisms. Methods: ADSC-CM was collected from ADSCs. The effects of intramuscular injection of ADSC-CM on cardiac function, cardiac apoptosis, and fibrosis examined by echocardiography, Evans blue/TTC staining, TUNEL assay, and Masson's trichrome staining in I/R-treated mice. We also examined the effects of ADSC-CM on apoptosis and fibrosis in H/R-treated H9c2 cells by annexin V/PI flow cytometry, TUNEL assay, and immunocytochemistry. Results: ADSC-CM treatment significantly reduced heart damage and fibrosis of I/R-treated mice and H/R-treated cardiomyocytes. In addition, the expression of apoptosis-related proteins, such as p53 upregulated modulator of apoptosis (PUMA), p-p53 and B-cell lymphoma 2 (BCL2), as well as the fibrosis-related proteins ETS-1, fibronectin and collagen 3, were significantly reduced by ADSC-CM treatment. Moreover, we demonstrated that ADSC-CM contains a large amount of miR-221/222, which can target and regulate PUMA or ETS-1 protein levels. Furthermore, the knockdown of PUMA and ETS-1 decreased the induction of apoptosis and fibrosis, respectively. MiR-221/222 overexpression achieved similar results. We also observed that cardiac I/R markedly increased apoptosis and fibrosis in miR-221/222 knockout (KO) mice, while ADSC-CM decreased these effects. The increased phosphorylation of p38 and NF-κB not only mediated myocardial apoptosis through the PUMA/p53/BCL2 pathway but also regulated fibrosis through the ETS-1/fibronectin/collagen 3 pathway. Conclusions: Overall, our results show that ADSC-CM attenuates cardiac apoptosis and fibrosis by reducing PUMA and ETS-1 expression, respectively. The protective effect is mediated via the miR-221/222/p38/NF-κB pathway. | en_US |
dc.publisher | IVYSPRING INT PUBL | en_US |
dc.relation.ispartof | Theranostics | en_US |
dc.subject | ADSC-CM; Ischemia/reperfusion injury; apoptosis; fibrosis; miR-221/222 | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.title | Conditioned medium from adipose-derived stem cells attenuates ischemia/reperfusion-induced cardiac injury through the microRNA-221/222/PUMA/ETS-1 pathway | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.7150/thno.52677 | - |
dc.identifier.pmid | 33537078 | - |
dc.identifier.scopus | 2-s2.0-85100246101 | - |
dc.identifier.isi | WOS:000604982100007 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/85100246101 | - |
dc.relation.pages | 3131 | en_US |
dc.relation.journalvolume | 11 | en_US |
dc.relation.journalissue | 7 | en_US |
dc.relation.pageend | 3149 | en_US |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.dept | Family Medicine | - |
crisitem.author.dept | Family Medicine-NTUH | - |
crisitem.author.dept | Center for Complementary and Integrated Medicine | - |
crisitem.author.dept | Anatomy and Cell Biology | - |
crisitem.author.orcid | 0000-0001-6748-5581 | - |
crisitem.author.orcid | 0000-0002-5227-8894 | - |
crisitem.author.orcid | 0000-0002-6498-4008 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
Appears in Collections: | 醫學檢驗暨生物技術學系 |
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