Effect of exercise on mRNA levels for growth factors in skeletal muscle of hemodialysis patients.
OBJECTIVE
Muscle mass and muscle mRNA levels for certain growth factors are reduced in maintenance hemodialysis (MHD) patients. This study tested the hypothesis that in MHD patients endurance exercise training (EET) increases mRNA levels for insulin-like growth factors and reduces myostatin mRNA.


METHODS
Biopsies of the right vastus lateralis muscle were performed before and at the end of 8.9 +/- 0.9 (SEM) weeks of EET in MHD patients. Muscle tissue was analyzed histologically by electron microscopy and for fiber cross-sectional area, and, in 8 pairs of biopsies, muscle was examined for mRNA levels for the following proteins: myostatin, insulin-like growth factor-I (IGF-I), IGF-I receptor (IGF-IR), IGF binding proteins (IGFBPs)-1, -2, -3, -4, and -5, and IGF-binding protein-related protein-1 (IGFBP-rP1).


METHODS
Outpatient MHD centers.


METHODS
This was a pilot study conducted in sedentary clinically stable MHD patients undergoing EET with no control group.


METHODS
EET that was carefully supervised by exercise trainers.


METHODS
Skeletal muscle mRNA levels, especially myostatin mRNA.


RESULTS
With EET, skeletal muscle myostatin mRNA decreased by 51%, mRNA levels increased significantly for IGF-IR (by 41%), IGFBP-2, -4, and -5, and IGFBP-rP1. IGF-I mRNA increased by 35%; this change was not significant. IGFBP-3 mRNA did not change, and IGFBP-1 mRNA was undetectable. There were mild to moderate alterations in skeletal muscle ultrastructure that did not change significantly with EET. Muscle fiber size, measured in 5 patients, did not change.


CONCLUSIONS
In MHD patients who undergo approximately 9 weeks of EET, skeletal muscle mRNA for myostatin decreases and mRNA for IGF-IR, IGFBPs -2, -4, and -5 and IGFBP-rP1 increases. These changes may indicate mechanisms by which EET improves muscle exercise capacity in MHD patients.
Kopple
Joel D
JD
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. jkopple@labiomed.org
Cohen
Arthur H
AH
Wang
Huiyuan
H
Qing
David
D
Tang
Zhanyung
Z
Fournier
Mario
M
Lewis
Michael
M
Casaburi
Richard
R
Storer
Thomas
T
D000328:Adult; D001706:Biopsy; D004044:Dietary Proteins / Q000008:administration & dosage; D002149:Energy Intake; D015444:Exercise / Q000502:physiology*; D005260:Female; D006003:Glycogen / Q000032:analysis; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000648:ultrastructure; D018656:Muscle Fibers, Fast-Twitch / Q000648:ultrastructure; D018657:Muscle Fibers, Slow-Twitch / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000648:ultrastructure; D055435:Myostatin; D010807:Physical Endurance / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis*; D017526:Receptor, IGF Type 1 / Q000235:genetics; D006435:Renal Dialysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
D004044:Dietary Proteins; D006133:Growth Substances; D018969:Insulin-Like Growth Factor Binding Proteins; C525911:MSTN protein, human; D055435:Myostatin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C102529:insulin-like growth factor binding protein-related protein 1; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D017526:Receptor, IGF Type 1