Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle.
The actions and receptor for ciliary neurotrophic factor (CNTF) are largely restricted to cells of the nervous system, although one of the CNTF receptor components, CNTFR alpha, is expressed by skeletal muscle. Here we show that the other CNTF receptor components, LIFR beta and gp130, are also expressed by skeletal muscle and that expression of all three CNTF receptor components is greatly increased in denervated muscle. In vivo, administration of CNTF activates these receptors on skeletal muscle by inducing receptor phosphorylation and immediate-early gene responses. Furthermore, CNTF reduces the denervation-induced atrophy of muscle and attenuates the reduced twitch and tetanic tensions that result from muscle denervation. Our findings reveal that, in addition to its known neurotrophic actions, CNTF exerts myotrophic effects by attenuating the morphological and functional changes associated with denervation of rat skeletal muscle.
Helgren
Maureen E
ME
Regeneron Pharmaceuticals, Incorporated, Tarrytown, New York 10591.
Squinto
Stephen P
SP
Davis
Heather L
HL
Parry
David J
DJ
Boulton
Teri G
TG
Heck
Carol S
CS
Zhu
Yuan
Y
Yancopoulos
George D
GD
Lindsay
Ronald M
RM
DiStefano
Peter S
PS
D000818:Animals; D015152:Blotting, Northern; D020934:Ciliary Neurotrophic Factor; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000502:physiology; D051381:Rats; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012584:Sciatic Nerve / Q000502:physiology*
D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins