title: α7β1Integrin regulation of gene transcription in skeletal muscle following an acute bout of eccentric exercise.
abstract: The α7β1integrin is concentrated at the costameres of skeletal muscle and provides a critical link between the actin cytoskeleton and laminin in the basement membrane. We previously demonstrated that expression of the α7BX2 integrin subunit (MCK:α7BX2) preserves muscle integrity and enhances myofiber cross-sectional area following eccentric exercise. The purpose of this study was to utilize gene expression profiling to reveal potential mechanisms by which the α7BX2-integrin contributes to improvements in muscle growth after exercise. A microarray analysis was performed using RNA extracted from skeletal muscle of wild-type or transgenic mice under sedentary conditions and 3 h following an acute bout of downhill running. Genes with false discovery rate probability values below the cutoff ofP< 0.05 (n= 73) were found to be regulated by either exercise or transgene expression. KEGG pathway analysis detected upregulation of genes involved in endoplasmic reticulum protein processing with integrin overexpression. Targeted analyses verified increased transcription ofRpl13a,Nosip,Ang,Scl7a5,Gys1,Ndrg2,Hspa5, andHsp40as a result of integrin overexpression alone or in combination with exercise (P< 0.05). A significant increase in HSPA5 protein and a decrease in CAAT-enhancer-binding protein homologous protein (CHOP) were detected in transgenic muscle (P< 0.05). In vitro knockdown experiments verified integrin-mediated regulation ofScl7a5The results from this study suggest that the α7β1integrin initiates transcription of genes that allow for protection from stress, including activation of a beneficial unfolded protein response and modulation of protein synthesis, both which may contribute to positive adaptations in skeletal muscle as a result of engagement in eccentric exercise.
authors.affiliation: Department of Kinesiology and Community Health and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Ziad S
authors.initials: ZS
authors.lastname: Mahmassani
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois; and.
authors.forename: Kook
authors.initials: K
authors.lastname: Son
authors.affiliation: Department of Kinesiology and Community Health and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Yair
authors.initials: Y
authors.lastname: Pincu
authors.affiliation: Department of Kinesiology and Community Health and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Munroe
authors.affiliation: Roy J. Carver Biotechnology Center, High Performance Biological Computing, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Jenny
authors.initials: J
authors.lastname: Drnevich
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois; and.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Kinesiology and Community Health and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois; mboppart@illinois.edu.
authors.forename: Marni D
authors.initials: MD
authors.lastname: Boppart
mesh_terms: D000818:Animals; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D016023:Integrins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods*; D010807:Physical Endurance / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D016023:Integrins; D009124:Muscle Proteins; C000621978:integrin alpha 7 beta 1, mouse
keywords: eccentric exercise; heat shock protein; integrin; microarray; stress