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MiR-34a-HK1 signal axis retards bone marrow mesenchymal stem cell senescence via ameliorating glycolytic metabolism.
- Source :
-
Stem cell research & therapy [Stem Cell Res Ther] 2024 Jul 30; Vol. 15 (1), pp. 238. Date of Electronic Publication: 2024 Jul 30. - Publication Year :
- 2024
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Abstract
- Background: Mesenchymal stem cells (MSCs) are one of the most widely studied adult stem cells, while MSC replicative senescence occurs with serial expansion in vitro. We determined whether miR-34a can regulate MSC senescence by directly targeting glycolytic key enzymes to influence glycolysis.<br />Methods: Detected the effects of miR-34a on MSC senescence and glycolytic metabolism through gene manipulation. Bioinformatics prediction and luciferase reporter assay were applied to confirm that HK1 is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting HK1 in MSC senescence was further explored by a cellular function recovery experiment.<br />Results: In the current study, we revealed that miR-34a over-expression exacerbated senescence-associated characteristics and impaired glycolytic metabolism. Then we identified hexokinase1 (HK1) as a direct target gene of miR-34a. And HK1 replenishment reversed MSC senescence and reinforced glycolysis. In addition, miR-34a-mediated MSC senescence and lower glycolytic levels were evidently rescued following the co-treatment with HK1 over-expression.<br />Conclusion: The miR-34a-HK1 signal axis can alleviate MSC senescence via enhancing glycolytic metabolism, which possibly provides a novel mechanism for MSC senescence and opens up new possibilities for delaying and suppressing the occurrence and development of aging and age-related diseases.<br /> (© 2024. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1757-6512
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cell research & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 39080798
- Full Text :
- https://doi.org/10.1186/s13287-024-03857-3