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| Status |
Public on May 08, 2024 |
| Title |
miR-765 induces angiogenesis by inhibiting dipeptidyl peptidase 4 and increasing fibroblast growth factor 2 |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Given that extracellular vesicles (EVs) secreted from stem cells contain angiogenic microRNAs (miRNAs), these EVs show equivalent angiogenic therapeutic effect to cell transplantation. This study aimed to identify the angiogenic miRNAs from several miRNAs involved in EVs secreted from stem cells. In human dental pulp stem cells (hDPSCs) under hypoxic culture, vascular endothelial growth factor (VEGF) involved in EVs increased. We hypothesized that angiogenic miRNAs increase in EVs that are secreted from hDPSCs under hypoxic culture compared with those under normoxic culture. In the first screening, the expression levels of miRNAs involved in EVs that were secreted from hDPSCs cultured under hypoxic and normoxic conditions were analyzed using miRNA array. In the second screening, 12 miRNAs were individually involved in EVs, and the growth of human aortic endothelial cells was assayed. In the third screening, miRNA-encapsulated EVs were injected in BALB/c mouse hindlimb ischemia model, followed by angiogenesis evaluation by blood flow analysis. Results showed that miR-765 is an angiogenic miRNA, targeting the 3′ untranslated region of dipeptidyl peptidase 4 (DPP4) and upregulating fibroblast growth factor 2 (FGF2) in vitro and in vivo. In conclusion, as an angiogenesis mechanism, miR-765 increased FGF2 expression levels by inhibiting DPP4.
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| Overall design |
To compare the expression levels of miRNAs in EVs isolated from the conditioned medium under normoxic conditions and hypoxic conditions and then analyzed the expression levels of miRNAs encapsulated in EVs by array analysis. Human dental pulp stem cells (hDPSCs) (2 × 105 cells/10 mL) were seeded into 10 cm dish in KBM ADSC-4 (#16030044; Kohjin Bio Co., Ltd.) and cultured 10 dishes of each for 7 days under normoxic and hypoxic conditions. The conditioned medium was concentrated using Amicon Ultra-15(#UFC901024, Merck Millipore Ltd.). Using the total exosome isolation reagent (from cell culture media)(#4478359, ThermoFisherScientific), we made pellets from the concentrated liquid of the conditioned medium. Next, microRNAs were isolated from the pellets by using the miRNeasy Mini Kit (#217004, Qiagen). The miRNA expression levels were analyzed using 3D-Gene® miRNA oligochips (Toray Industries, Inc.)
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| Contributor(s) |
Ueno K, Suzuki R, Kurazumi H, Mizoguchi T, Tanaka T, Hamano K |
| Citation missing |
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| Submission date |
May 10, 2023 |
| Last update date |
May 08, 2024 |
| Contact name |
Satoshi Kondo |
| Organization name |
Toray Industries,Inc.
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| Street address |
10-1 tebiro 6-chome
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| City |
Kamakura |
| State/province |
Kanagawa |
| ZIP/Postal code |
248-8555 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA971178 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232178_RAW.tar |
130.0 Kb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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