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| Author(s): |
Tatiana Emy Koike
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2021-11-08 |
| Examining board members: |
Elen Haruka Miyabara;
Cecilia Helena de Azevedo Gouveia Ferreira;
Mariana Kiomy Osako;
Marco Carlos Uchida
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| Advisor: | Elen Haruka Miyabara |
| Abstract | |
Skeletal muscle regeneration is a highly orchestrated process that involves the activation and proliferation of muscle stem cells known as satellite cells. Proliferating satellite cellsmyogenic precursor cellsdifferentiate and fuse with each other, leading to the formation of multinucleated myotubes. A subpopulation of activated satellite cells self-renews to replenish the satellite cell pool. β2-adrenergic signaling is implicated in muscle regeneration; however, its role in satellite cell function is unclear. This study investigates the role of the β2 adrenoceptor (Adrβ2) in satellite cell self-renewal and proliferation and myoblast differentiation using Adrβ2 knockout (β2ko) mice. The in vitro results showed a significant reduction in the number of proliferating satellite cells (at 3 days post-injury [dpi]), self-renewed satellite cells (at 30 dpi), and regenerating eMyHC+ myofibers (at 10 dpi) in the regenerating muscle of β2ko mice. The in vitro results demonstrated a lower number of proliferating myoblasts, an increase in the gene expression of the cell cycle inhibitor Cdkn1a and Notch pathway components (Notch1, Delta-like1, and RBPJ), an increase in Notch signaling, and a decrease in the expression of miR-326-3p in proliferating myoblasts from β2ko mice. There was a decrease in the number of myogenin-positive nuclei in the differentiating myofibers, and a lower fusion index in differentiating myoblasts from β2ko mice. Furthermore, there was a decrease in the gene expression of Akt/mTOR components (Akt and p70S6k) and Wnt/ β-catenin components (β-catenin and Lef1), decreased expression of proteins p70S6k (ser371) and β-catenin, reduced activity of the Wnt/β-catenin signaling pathway, and decreased expression of miRNAs 326-3p and 374b-5p in differentiating myoblasts from β2ko mice. These results suggest that Adrβ2 influences satellite cell self-renewal and myoblast proliferation mediated by Notch signaling and miR-326-3p expression, and myoblast differentiation. (AU) | |
| FAPESP's process: | 17/09069-4 - The influence of beta 2-adrenoceptor in satellite cell function |
| Grantee: | Tatiana Emy Koike |
| Support Opportunities: | Scholarships in Brazil - Doctorate |