miR-10a restores human mesenchymal stem cell differentiation by repressing KLF4
| Autor: | Shiming Liu, Dong-Cheng Zhang, Min-Sheng Chen, Jiao Li, Zhenhui Zhang, Yun Zhong, Jun Dong, Xiang-Yu You |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Senescence
Adult Male Adolescent Physiology Cellular differentiation Clinical Biochemistry Kruppel-Like Transcription Factors Down-Regulation Biology Kruppel-Like Factor 4 Young Adult Downregulation and upregulation Original Research Articles Humans 3' Untranslated Regions Cellular Senescence Aged Aged 80 and over Nucleotides Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Molecular biology Cell biology Up-Regulation MicroRNAs KLF4 Adipogenesis Mutation Female Mesenchymal stem cell differentiation Cell aging |
| Zdroj: | Journal of Cellular Physiology |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | miRNAs have recently been shown to play a significant role in human aging. However, data demonstrating the effects of aging-related miRNAs in human mesenchymal stem cells (hMSCs) are limited. We observed that hMSC differentiation decreased with aging. We also identified that miR-10a expression was significantly decreased with age by comparing the miRNA expression of hMSCs derived from young and aged individuals. Therefore, we hypothesized that the downregulation of miR-10a may be associated with the decreased differentiation capability of hMSCs from aged individuals. Lentiviral constructs were used to up- or downregulate miR-10a in young and old hMSCs. Upregulation of miR-10a resulted in increased differentiation to adipogenic, osteogenic, and chondrogenic lineages and in reduced cell senescence. Conversely, downregulation of miR-10a resulted in decreased cell differentiation and increased cell senescence. A chimeric luciferase reporter system was generated, tagged with the full-length 3′-UTR region of KLF4 harboring the seed-matched sequence with or without four nucleotide mutations. These constructs were cotransfected with the miR-10a mimic into cells. The luciferase activity was significantly repressed by the miR-10a mimic, proving the direct binding of miR-10a to the 3′-UTR of KLF4. Direct suppression of KLF4 in aged hMSCs increased cell differentiation and decreased cell senescence. In conclusion, miR-10a restores the differentiation capability of aged hMSCs through repression of KLF4. Aging-related miRNAs may have broad applications in the restoration of cell dysfunction caused by aging. J. Cell. Physiol. 228: 2324–2336, 2013. © The Authors. Published by Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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