| RRC ID |
81281
|
| Author |
Ueno K, Kurazumi H, Suzuki R, Yanagihara M, Mizoguchi T, Harada T, Morikage N, Hamano K.
|
| Title |
miR-709 exerts an angiogenic effect through a FGF2 upregulation induced by a GSK3B downregulation.
|
| Journal |
Sci Rep
|
| Abstract |
The aim of this study was to identify angiogenic microRNAs (miRNAs) that could be used in the treatment of hindlimb ischemic tissues. miRNAs contained in extracellular vesicles (EVs) deriving from the plasma were analyzed in C57BL/6 mice, which have ischemia tolerance, and in BALB/c mice without ischemia tolerance as part of a hindlimb ischemia model; as a result 43 angiogenic miRNA candidates were identified. An aortic ring assay was employed by using femoral arteries isolated from BALC/c mice and EVs containing miRNA; as a result, the angiogenic miRNA candidates were limited to 14. The blood flow recovery was assessed after injecting EVs containing miRNA into BALB/c mice with hindlimb ischemia, and miR-709 was identified as a promising angiogenic miRNA. miR-709-encapsulating EVs were found to increase the expression levels of the fibroblast growth factor 2 (FGF2) mRNA in the thigh tissues of hindlimb ischemia model BALB/c mice. miR-709 was also found to bind to the 3'UTR of glycogen synthase kinase 3 beta (GSK3B) in three places. GSK3B-knockdown human artery-derived endothelial cells were found to express high levels of FGF2, and were characterized by increased cell proliferation. These findings indicate that miR-709 induces an upregulation of FGF2 through the downregulation of GSK3B.
|
| Volume |
14(1)
|
| Pages |
11372
|
| Published |
2024-5-18
|
| DOI |
10.1038/s41598-024-62340-4
|
| PII |
10.1038/s41598-024-62340-4
|
| PMID |
38762650
|
| PMC |
PMC11102560
|
| MeSH |
3' Untranslated Regions
Animals
Cell Proliferation
Disease Models, Animal
Down-Regulation
Endothelial Cells / metabolism
Extracellular Vesicles / metabolism
Fibroblast Growth Factor 2* / genetics
Fibroblast Growth Factor 2* / metabolism
Glycogen Synthase Kinase 3 beta* / genetics
Glycogen Synthase Kinase 3 beta* / metabolism
Hindlimb* / blood supply
Humans
Ischemia* / genetics
Ischemia* / metabolism
Male
Mice
Mice, Inbred BALB C*
Mice, Inbred C57BL
MicroRNAs* / genetics
MicroRNAs* / metabolism
Neovascularization, Physiologic* / genetics
Up-Regulation
|
| IF |
3.998
|
| Resource |
| Human and Animal Cells |
293T(RCB2202) |
