Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing
Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-r...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/4/345 |
| _version_ | 1827718160727408640 |
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| author | Maria Borja-Gonzalez Jose C. Casas-Martinez Brian McDonagh Katarzyna Goljanek-Whysall |
| author_facet | Maria Borja-Gonzalez Jose C. Casas-Martinez Brian McDonagh Katarzyna Goljanek-Whysall |
| author_sort | Maria Borja-Gonzalez |
| collection | DOAJ |
| description | Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H<sub>2</sub>O<sub>2</sub>, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration. |
| first_indexed | 2024-03-10T20:17:27Z |
| format | Article |
| id | doaj.art-88227c1db1dc4707b0144164e1084e31 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T20:17:27Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-88227c1db1dc4707b0144164e1084e312023-11-19T22:27:15ZengMDPI AGAntioxidants2076-39212020-04-019434510.3390/antiox9040345Inflamma-miR-21 Negatively Regulates Myogenesis during AgeingMaria Borja-Gonzalez0Jose C. Casas-Martinez1Brian McDonagh2Katarzyna Goljanek-Whysall3School of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, IrelandSchool of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, IrelandSchool of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, IrelandSchool of Medicine, Physiology, National University of Ireland, H91 W5P7 Galway, IrelandAgeing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H<sub>2</sub>O<sub>2</sub>, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.https://www.mdpi.com/2076-3921/9/4/345microRNAmuscleagingsarcopeniacachexiaregeneration |
| spellingShingle | Maria Borja-Gonzalez Jose C. Casas-Martinez Brian McDonagh Katarzyna Goljanek-Whysall Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing Antioxidants microRNA muscle aging sarcopenia cachexia regeneration |
| title | Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing |
| title_full | Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing |
| title_fullStr | Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing |
| title_full_unstemmed | Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing |
| title_short | Inflamma-miR-21 Negatively Regulates Myogenesis during Ageing |
| title_sort | inflamma mir 21 negatively regulates myogenesis during ageing |
| topic | microRNA muscle aging sarcopenia cachexia regeneration |
| url | https://www.mdpi.com/2076-3921/9/4/345 |
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