Work-induced changes in skeletal muscle IGF-1 and myostatin gene expression in uremia.
Resistance to growth hormone (GH)-induced insulin-like growth factor-1 (IGF-1) gene expression contributes to uremic muscle wasting. Since exercise stimulates muscle IGF-1 expression independent of GH, we tested whether work overload (WO) could increase skeletal muscle IGF-1 expression in uremia and thus bypass the defective GH action. Furthermore, to provide insight into the mechanism of uremic wasting and the response to exercise we examined myostatin expression. Unilateral plantaris muscle WO was initiated in uremic and pairfed (PF) normal rats by ablation of a gastrocnemius tendon and adjoining part of this muscle with the contralateral plantaris as a control. Some rats were GH treated for 7 days. WO led to similar gains in plantaris weight in both groups and corrected the uremic muscle atrophy. GH increased plantaris IGF-1 mRNA >twofold in PF rats but the response in uremia was severely attenuated. WO increased the IGF-1 mRNA levels significantly in both uremic and PF groups, albeit less brisk in uremia; however, after 7 days IGF-1 mRNA levels were elevated similarly, >2-fold, in both groups. In the atrophied uremic plantaris muscle basal myostatin mRNA levels were increased significantly and normalized after an increase in WO suggesting a myostatin role in the wasting process. In the hypertrophied uremic left ventricle the basal myostatin mRNA levels were reduced and likely favor the cardiac hypertrophy. Together the findings provide insight into the mechanisms of skeletal muscle wasting in uremia and the hypertrophic response to exercise, and suggest that alterations in the balance between IGF-1 and myostatin play an important role in these processes.
Sun
D F
DF
Research Service Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
Chen
Y
Y
Rabkin
R
R
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004351:Drug Resistance; D015870:Gene Expression; D013006:Growth Hormone / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D006984:Hypertrophy; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D055435:Myostatin; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014511:Uremia / Q000150:complications / Q000503:physiopathology*
C525913:Mstn protein, rat; D055435:Myostatin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003404:Creatinine