Increased Expression of CNTF Receptor a in Denervated Human Skeletal Muscle

The functional receptor for ciliary neurotrophic factor (CNTF) is comprised of a CNTF binding entity termed CNTF receptor a (CNTFRα), and 2 signaling molecules called LIF receptor β and gpl30. CNTFRα can be released from the cell surface; the soluble form can confer CNTF responsiveness to cells. CNTFRα has recently been localized to several nonneuronal cell types including rat skeletal muscle fibers. In this study we examined the expression pattern of CNTFRa 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, CNTFRα 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, CNTFRα transcripts were detected in the sarcoplasm of both normal sized and atrophic muscle fibers. In addition, soluble CNTFRa was elevated 4.4-fold in the urine of ALS patients compared to normal adults. These results suggest that the expression of CNTFRα in human skeletal muscle fibers is regulated by innervation. This regulation appears to be selective, because CNTFRα mRNA was not increased in dystrophic human muscle. Increased CNTFRα could confer higher sensitivity to CNTF during neurodegeneration or nerve fiber regeneration.