| First Author | van der Pijl R | Year | 2018 |
| Journal | J Cachexia Sarcopenia Muscle | Volume | 9 |
| Issue | 5 | Pages | 947-961 |
| PubMed ID | 29978560 | Mgi Jnum | J:302932 |
| Mgi Id | MGI:6510932 | Doi | 10.1002/jcsm.12319 |
| Citation | van der Pijl R, et al. (2018) Titin-based mechanosensing modulates muscle hypertrophy. J Cachexia Sarcopenia Muscle 9(5):947-961 |
| abstractText | BACKGROUND: Titin is an elastic sarcomeric filament that has been proposed to play a key role in mechanosensing and trophicity of muscle. However, evidence for this proposal is scarce due to the lack of appropriate experimental models to directly test the role of titin in mechanosensing. METHODS: We used unilateral diaphragm denervation (UDD) in mice, an in vivo model in which the denervated hemidiaphragm is passively stretched by the contralateral, innervated hemidiaphragm and hypertrophy rapidly occurs. RESULTS: In wildtype mice, the denervated hemidiaphragm mass increased 48 +/- 3% after 6 days of UDD, due to the addition of both sarcomeres in series and in parallel. To test whether titin stiffness modulates the hypertrophy response, RBM20(DeltaRRM) and Ttn(DeltaIAjxn) mouse models were used, with decreased and increased titin stiffness, respectively. RBM20(DeltaRRM) mice (reduced stiffness) showed a 20 +/- 6% attenuated hypertrophy response, whereas the Ttn(DeltaIAjxn) mice (increased stiffness) showed an 18 +/- 8% exaggerated response after UDD. Thus, muscle hypertrophy scales with titin stiffness. Protein expression analysis revealed that titin-binding proteins implicated previously in muscle trophicity were induced during UDD, MARP1 & 2, FHL1, and MuRF1. CONCLUSIONS: Titin functions as a mechanosensor that regulates muscle trophicity. |
