Titin-based mechanosensing modulates muscle hypertrophy

Robbert van der Pijl, Joshua Strom, Stefan Conijn, Johan Lindqvist, Siegfried Labeit, Hendrikus "Henk" Granzier, Coen Ottenheijm

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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, RBM20ΔRRM and TtnΔIAjxn mouse models were used, with decreased and increased titin stiffness, respectively. RBM20ΔRRM mice (reduced stiffness) showed a 20 ± 6% attenuated hypertrophy response, whereas the TtnΔIAjxn 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.

Original languageEnglish (US)
JournalJournal of Cachexia, Sarcopenia and Muscle
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Connectin
Hypertrophy
Muscles
Denervation
Diaphragm
Sarcomeres
Carrier Proteins
Theoretical Models

Keywords

  • Denervation
  • Diaphragm
  • Hypertrophy
  • Mechanosensing
  • Muscle stretch
  • Titin

ASJC Scopus subject areas

  • Biophysics
  • Applied Microbiology and Biotechnology
  • Orthopedics and Sports Medicine
  • Physiology (medical)

Cite this

van der Pijl, R., Strom, J., Conijn, S., Lindqvist, J., Labeit, S., Granzier, H. H., & Ottenheijm, C. (Accepted/In press). Titin-based mechanosensing modulates muscle hypertrophy. Journal of Cachexia, Sarcopenia and Muscle. https://doi.org/10.1002/jcsm.12319

Titin-based mechanosensing modulates muscle hypertrophy. / van der Pijl, Robbert; Strom, Joshua; Conijn, Stefan; Lindqvist, Johan; Labeit, Siegfried; Granzier, Hendrikus "Henk"; Ottenheijm, Coen.

In: Journal of Cachexia, Sarcopenia and Muscle, 01.01.2018.

Research output: Contribution to journalArticle

van der Pijl, Robbert ; Strom, Joshua ; Conijn, Stefan ; Lindqvist, Johan ; Labeit, Siegfried ; Granzier, Hendrikus "Henk" ; Ottenheijm, Coen. / Titin-based mechanosensing modulates muscle hypertrophy. In: Journal of Cachexia, Sarcopenia and Muscle. 2018.
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