{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:59:04Z","timestamp":1792295944825,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL121500"],"award-info":[{"award-number":["R01HL121500"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used unilateral diaphragm denervation (UDD) in mice, an <jats:italic>in vivo<\/jats:italic> model in which the denervated hemidiaphragm is passively stretched by the contralateral, innervated hemidiaphragm and hypertrophy rapidly occurs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In wildtype mice, the denervated hemidiaphragm mass increased 48\u00a0\u00b1\u00a03% 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<jats:sup>\u0394RRM<\/jats:sup> and Ttn<jats:sup>\u0394IAjxn<\/jats:sup> mouse models were used, with decreased and increased titin stiffness, respectively. RBM20<jats:sup>\u0394RRM<\/jats:sup> mice (reduced stiffness) showed a 20\u00a0\u00b1\u00a06% attenuated hypertrophy response, whereas the Ttn<jats:sup>\u0394IAjxn<\/jats:sup> mice (increased stiffness) showed an 18\u00a0\u00b1\u00a08% exaggerated response after UDD. Thus, muscle hypertrophy scales with titin stiffness. Protein expression analysis revealed that titin\u2010binding proteins implicated previously in muscle trophicity were induced during UDD, MARP1 &amp; 2, FHL1, and MuRF1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Titin functions as a mechanosensor that regulates muscle trophicity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12319","type":"journal-article","created":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T03:11:27Z","timestamp":1530846687000},"page":"947-961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Titin\u2010based mechanosensing modulates muscle hypertrophy"],"prefix":"10.1002","volume":"9","author":[{"given":"Robbert","family":"van der Pijl","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine University of Arizona  Tucson AZ USA"},{"name":"Dept of Physiology VU University Medical Center  Amsterdam The 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