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Title:Investigation of a role for the α7 integrin as a mechanotransducer of hypertrophic signaling in skeletal muscle
Author(s):Mahmassani, Ziad S.
Advisor(s):Boppart, Marni M.
Department / Program:Kinesiology & Community Health
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):α7 integrin
intrinsic regulator of strain-induced hypertrophic signaling
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.
Issue Date:2013-02-03
Rights Information:Copyright 2012 Ziad Mahmassani
Date Available in IDEALS:2013-02-03
Date Deposited:2012-12

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