{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/42131"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/42131","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Investigation of a role for the α7 integrin as a mechanotransducer of hypertrophic signaling in skeletal muscle","abstract":"The α7β1 integrin is a transmembrane protein in skeletal muscle which serves as a focal adhesion at costameres of skeletal muscle, providing a critical link between the actin cytoskeleton inside the cell with laminin in the basement membrane of the extracellular matrix. Previous research has demonstrated that overexpression of the α7 integrin accelerates the muscle growth response to eccentric exercise compared to wild type controls. PURPOSE: The goal of this project was to elucidate a role for the α7 integrin as a mechanotransducer and intrinsic regulator of hypertrophic signaling in response to mechanical strain. METHODS: Primary myoblasts extracted from wild type (WT) mice were developed into myotubes in culture to determine the hypertrophic signaling response to mechanical strain. Primary myoblasts from α7 knockout (KO) mice were used as controls for these experiments. Further experimentation employed transient transfection of WT myoblasts with a α7 integrin plasmid transgene containing a muscle creatine kinase and myosin heavy chain promoter (MHCK7) to induce α7 integrin expression. Transfected myotubes were subjected to overnight incubations in wortmannin with the goal of inhibiting any potential autocrine-mediated growth factor signaling pathway through PI3K inhibition. RESULTS: Lack of α7 integrin was verified in KO cells. In WT, mechanical strain increased α7 integrin protein at 3 PS on both substrates compared to control (P<0.05; 1.8-fold collagen, 3-fold laminin). Phosphorylation of p70 S6K was increased 5-fold only on laminin at 3 PS (P<0.05). In contrast, no change in p70 S6K phosphorylation was observed in KO cells on either substrate. Interestingly, mTOR phosphorylation was not significantly altered in WT myotubes, and no change was observed in KO myotubes in response to strain. Transgenic overexpression of the α7 integrin in myotubes resulted in a trend toward increased activation of hypertrophic signaling compared to controls, which did not reach statistical significance. CONCLUSION: This study provides evidence that the α7 integrin is upregulated in response to mechanical strain and is inconclusive on whether the α7 integrin is an intrinsic regulator of strain-induced hypertrophic signaling.","abstract_html":"The α7β1 integrin is a transmembrane protein in skeletal muscle which serves as a focal adhesion at costameres of skeletal muscle, providing a critical link between the actin cytoskeleton inside the cell with laminin in the basement membrane of the extracellular matrix. Previous research has demonstrated that overexpression of the α7 integrin accelerates the muscle growth response to eccentric exercise compared to wild type controls. PURPOSE: The goal of this project was to elucidate a role for the α7 integrin as a mechanotransducer and intrinsic regulator of hypertrophic signaling in response to mechanical strain. METHODS: Primary myoblasts extracted from wild type (WT) mice were developed into myotubes in culture to determine the hypertrophic signaling response to mechanical strain. Primary myoblasts from α7 knockout (KO) mice were used as controls for these experiments. Further experimentation employed transient transfection of WT myoblasts with a α7 integrin plasmid transgene containing a muscle creatine kinase and myosin heavy chain promoter (MHCK7) to induce α7 integrin expression. Transfected myotubes were subjected to overnight incubations in wortmannin with the goal of inhibiting any potential autocrine-mediated growth factor signaling pathway through PI3K inhibition. RESULTS: Lack of α7 integrin was verified in KO cells. In WT, mechanical strain increased α7 integrin protein at 3 PS on both substrates compared to control (P&lt;0.05; 1.8-fold collagen, 3-fold laminin). Phosphorylation of p70 S6K was increased 5-fold only on laminin at 3 PS (P&lt;0.05). In contrast, no change in p70 S6K phosphorylation was observed in KO cells on either substrate. Interestingly, mTOR phosphorylation was not significantly altered in WT myotubes, and no change was observed in KO myotubes in response to strain. Transgenic overexpression of the α7 integrin in myotubes resulted in a trend toward increased activation of hypertrophic signaling compared to controls, which did not reach statistical significance. CONCLUSION: This study provides evidence that the α7 integrin is upregulated in response to mechanical strain and is inconclusive on whether the α7 integrin is an intrinsic regulator of strain-induced hypertrophic signaling.","abstract_has_math":false,"creators":["Mahmassani, Ziad S."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Kinesiology","degree_department":null,"school":null,"contributors":["Boppart, Marni M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-02-03T19:16:42Z","date_published":"2013-02-03T19:16:42Z","updated_at":"2026-07-22T22:25:31Z","subjects":["α7 integrin","intrinsic regulator of strain-induced hypertrophic signaling","mechanotransduction"],"languages":["en"],"rights":["Copyright 2012 Ziad Mahmassani"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/42131","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Boppart, Marni M."]},{"key":"dc:creator","label":"Author","values":["Mahmassani, Ziad S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-02-03T19:16:42Z","2015-02-03T11:01:03Z","2012-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Kinesiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M.S."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["α7 integrin","intrinsic regulator of strain-induced hypertrophic signaling","mechanotransduction"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2012 Ziad Mahmassani"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/42131"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The α7β1 integrin is a transmembrane protein in skeletal muscle which serves as a focal adhesion at costameres of skeletal muscle, providing a critical link between the actin cytoskeleton inside the cell with laminin in the basement membrane of the extracellular matrix. Previous research has demonstrated that overexpression of the α7 integrin accelerates the muscle growth response to eccentric exercise compared to wild type controls. PURPOSE: The goal of this project was to elucidate a role for the α7 integrin as a mechanotransducer and intrinsic regulator of hypertrophic signaling in response to mechanical strain. METHODS: Primary myoblasts extracted from wild type (WT) mice were developed into myotubes in culture to determine the hypertrophic signaling response to mechanical strain. Primary myoblasts from α7 knockout (KO) mice were used as controls for these experiments. Further experimentation employed transient transfection of WT myoblasts with a α7 integrin plasmid transgene containing a muscle creatine kinase and myosin heavy chain promoter (MHCK7) to induce α7 integrin expression. Transfected myotubes were subjected to overnight incubations in wortmannin with the goal of inhibiting any potential autocrine-mediated growth factor signaling pathway through PI3K inhibition. RESULTS: Lack of α7 integrin was verified in KO cells. In WT, mechanical strain increased α7 integrin protein at 3 PS on both substrates compared to control (P<0.05; 1.8-fold collagen, 3-fold laminin). Phosphorylation of p70 S6K was increased 5-fold only on laminin at 3 PS (P<0.05). In contrast, no change in p70 S6K phosphorylation was observed in KO cells on either substrate. Interestingly, mTOR phosphorylation was not significantly altered in WT myotubes, and no change was observed in KO myotubes in response to strain. Transgenic overexpression of the α7 integrin in myotubes resulted in a trend toward increased activation of hypertrophic signaling compared to controls, which did not reach statistical significance. CONCLUSION: This study provides evidence that the α7 integrin is upregulated in response to mechanical strain and is inconclusive on whether the α7 integrin is an intrinsic regulator of strain-induced hypertrophic signaling.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2012-12-10T20:03:19Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Mahmassani_Ziad.pdf: 2983170 bytes, checksum: fa7214949fe0905f66893c4fbae6a3d6 (MD5)","Made available in DSpace on 2013-02-03T19:16:42Z (GMT). No. of bitstreams: 2 Ziad_Mahmassani.pdf: 2976797 bytes, checksum: 7ff2402dec4c9fb50944a4341dfab0fc (MD5) license.txt: 4065 bytes, checksum: 097e4265718891a16f37502cde91b6ea (MD5)","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Seth Robbins (srobbins@illinois.edu) on 2013-02-03T19:18:57Z Item is restricted until 2015-02-03T19:18:53Z","Restriction data tranferred 2014-07-01T11:11:51-05:00 Original Data Group with Access UIUC Users [automated] Release Date: 2015-02-03 13:18:53 UTC Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 42078 on 2015-02-03T11:01:03Z."]},{"key":"dc:title","label":"Title","values":["Investigation of a role for the α7 integrin as a mechanotransducer of hypertrophic signaling in skeletal muscle"]}]}],"canonical_facts":{"dc:contributor":["Boppart, Marni M."],"dc:creator":["Mahmassani, Ziad S."],"dc:date":["2013-02-03T19:16:42Z","2015-02-03T11:01:03Z","2012-12"],"dc:description":["The α7β1 integrin is a transmembrane protein in skeletal muscle which serves as a focal adhesion at costameres of skeletal muscle, providing a critical link between the actin cytoskeleton inside the cell with laminin in the basement membrane of the extracellular matrix. Previous research has demonstrated that overexpression of the α7 integrin accelerates the muscle growth response to eccentric exercise compared to wild type controls. PURPOSE: The goal of this project was to elucidate a role for the α7 integrin as a mechanotransducer and intrinsic regulator of hypertrophic signaling in response to mechanical strain. METHODS: Primary myoblasts extracted from wild type (WT) mice were developed into myotubes in culture to determine the hypertrophic signaling response to mechanical strain. Primary myoblasts from α7 knockout (KO) mice were used as controls for these experiments. Further experimentation employed transient transfection of WT myoblasts with a α7 integrin plasmid transgene containing a muscle creatine kinase and myosin heavy chain promoter (MHCK7) to induce α7 integrin expression. Transfected myotubes were subjected to overnight incubations in wortmannin with the goal of inhibiting any potential autocrine-mediated growth factor signaling pathway through PI3K inhibition. RESULTS: Lack of α7 integrin was verified in KO cells. In WT, mechanical strain increased α7 integrin protein at 3 PS on both substrates compared to control (P<0.05; 1.8-fold collagen, 3-fold laminin). Phosphorylation of p70 S6K was increased 5-fold only on laminin at 3 PS (P<0.05). In contrast, no change in p70 S6K phosphorylation was observed in KO cells on either substrate. Interestingly, mTOR phosphorylation was not significantly altered in WT myotubes, and no change was observed in KO myotubes in response to strain. Transgenic overexpression of the α7 integrin in myotubes resulted in a trend toward increased activation of hypertrophic signaling compared to controls, which did not reach statistical significance. CONCLUSION: This study provides evidence that the α7 integrin is upregulated in response to mechanical strain and is inconclusive on whether the α7 integrin is an intrinsic regulator of strain-induced hypertrophic signaling.","Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2012-12-10T20:03:19Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Mahmassani_Ziad.pdf: 2983170 bytes, checksum: fa7214949fe0905f66893c4fbae6a3d6 (MD5)","Made available in DSpace on 2013-02-03T19:16:42Z (GMT). No. of bitstreams: 2 Ziad_Mahmassani.pdf: 2976797 bytes, checksum: 7ff2402dec4c9fb50944a4341dfab0fc (MD5) license.txt: 4065 bytes, checksum: 097e4265718891a16f37502cde91b6ea (MD5)","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Seth Robbins (srobbins@illinois.edu) on 2013-02-03T19:18:57Z Item is restricted until 2015-02-03T19:18:53Z","Restriction data tranferred 2014-07-01T11:11:51-05:00 Original Data Group with Access UIUC Users [automated] Release Date: 2015-02-03 13:18:53 UTC Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 42078 on 2015-02-03T11:01:03Z."],"dc:identifier":["http://hdl.handle.net/2142/42131"],"dc:language":["en"],"dc:rights":["Copyright 2012 Ziad Mahmassani"],"dc:subject":["α7 integrin","intrinsic regulator of strain-induced hypertrophic signaling","mechanotransduction"],"dc:title":["Investigation of a role for the α7 integrin as a mechanotransducer of hypertrophic signaling in skeletal muscle"],"dc:type":["text"],"thesis:degree_discipline":["Kinesiology"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["M.S."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:31Z"}