Increased expression of CNTF receptor alpha in denervated human skeletal muscle.

The functional receptor for ciliary neurotrophic factor (CNTF) is comprised of a CNTF binding entity termed CNTF receptor alpha (CNTFRalpha), and 2 signaling molecules called LIF receptor beta and gp130. CNTFRalpha can be released from the cell surface; the soluble form can confer CNTF responsiveness to cells. CNTFRalpha has recently been localized to several nonneuronal cell types including rat skeletal muscle fibers. In this study we examined the expression pattern of CNTFRalpha in normal, denervated and dystrophic human muscle. In muscle biopsies from 12 normal subjects, 16 cases of neurogenic muscular atrophy, 4 cases of Duchenne muscular dystrophy, and 4 cases of limb girdle dystrophy, CNTFRalpha mRNA levels were determined by Northern blotting. Transcript levels were significantly increased in cases of neurogenic atrophy compared to normal controls and dystrophic muscle. By nonradioactive in situ hybridization, CNTFRalpha transcripts were detected in the sarcoplasm of both normal sized and atrophic muscle fibers. In addition, soluble CNTFRalpha was elevated 4.4-fold in the urine of ALS patients compared to normal adults. These results suggest that the expression of CNTFRalpha in human skeletal muscle fibers is regulated by innervation. This regulation appears to be selective, because CNTFRalpha mRNA was not increased in dystrophic human muscle. Increased CNTFRalpha could confer higher sensitivity to CNTF during neurodegeneration or nerve fiber regeneration.