| First Author | Rønning SB | Year | 2020 |
| Journal | Front Cell Dev Biol | Volume | 8 |
| Pages | 730 | PubMed ID | 32850844 |
| Mgi Jnum | J:309869 | Mgi Id | MGI:6752271 |
| Doi | 10.3389/fcell.2020.00730 | Citation | Ronning SB, et al. (2020) Syndecan-4(-/-) Mice Have Smaller Muscle Fibers, Increased Akt/mTOR/S6K1 and Notch/HES-1 Pathways, and Alterations in Extracellular Matrix Components. Front Cell Dev Biol 8:730 |
| abstractText | Background: Extracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4(-/-) mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4(-/-) muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise. Methods: Tibialis anterior (TA) muscles from sedentary and exercised syndecan-4(-/-) and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting. Results: Compared to WT, we found that syndecan-4(-/-) mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4(-/-) had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4(-/-) mice. Conclusion: Altogether our data suggest an important role of syndecan-4 in muscle development. |
