{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:32:33Z","timestamp":1774567953070,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["CBET 1714778"],"award-info":[{"award-number":["CBET 1714778"]}]},{"name":"National Science Foundation","award":["CBET 2224902"],"award-info":[{"award-number":["CBET 2224902"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm\u2014a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory uncovered that stretching the diaphragm in either the longitudinal or transverse direction activates distinct mechanotransduction pathways. This indicates that signaling pathways in the diaphragm muscle are regulated in an anisotropic manner. In this review paper, we discussed the underlying mechanisms that regulate the anisotropic signaling pathways in the diaphragmatic muscle, emphasizing the mechanical role of cytoskeletal proteins in this context. Furthermore, we explored the regulatory mechanisms governing mechanosensitive gene transcription, including microRNAs (mechanomiRs), within the diaphragm muscle. Finally, we examined potential links between anisotropic signaling in the diaphragm muscle and various skeletal muscle disorders.<\/jats:p>","DOI":"10.3390\/genes16080968","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T07:56:06Z","timestamp":1755590166000},"page":"968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechano-Signal Transduction Pathways of the Diaphragmatic Muscle and Role of Cytoskeleton"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-4856","authenticated-orcid":false,"given":"Junaith S.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Laboratory of Muscle and Nerve, Department of Diagnostic and Health Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Center for Muscle, Metabolism and Neuropathology, Division of Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Integrated Biomedical Sciences Graduate Program, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia S.","family":"Pardo","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aladin M.","family":"Boriek","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrm2597","article-title":"Mechanotransduction gone awry","volume":"10","author":"Jaalouk","year":"2009","journal-title":"Nat. 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