title: Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.
abstract: Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.
  
  
  OBJECTIVE
  The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.
  
  
  METHODS
  Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression.
  
  
  RESULTS
  We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p < 0.05); while vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat stress repressed PGC-1α (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05).
  
  
  CONCLUSIONS
  These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Petrie
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Kimball
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Colleen L
authors.initials: CL
authors.lastname: McHenry
authors.affiliation: Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.|Department of Veterans Affairs, VA Medical Center, Iowa City, Iowa, United States of America.
authors.forename: Manish
authors.initials: M
authors.lastname: Suneja
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Chu-Ling
authors.initials: CL
authors.lastname: Yen
authors.affiliation: Department of Biochemistry, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Arpit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America.|Department of Veterans Affairs, VA Medical Center, Iowa City, Iowa, United States of America.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Shields
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015444:Exercise / Q000502:physiology; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013314:Stress, Mechanical; D013312:Stress, Physiological / Q000235:genetics; D019415:Torque; D014732:Vibration; D055815:Young Adult