INCREASED EXPRESSION OF CNTF RECEPTOR-ALPHA IN DENERVATED HUMAN SKELETAL-MUSCLE

The functional receptor for ciliary neurotrophic factor (CNTF) is comp rised of a CNTF binding entity termed CNTF receptor alpha (CNTFR alpha ), and 2 signaling molecules called LIF receptor beta and gp130. CNTFR alpha can be released from the cell surface: the soluble form can con fer CNTF responsiveness to cells. CNTFR alpha has recently been locali zed to several nonneuronal cell types including rat skeletal muscle fi bers. In this study we examined the expression pattern of CNTFR alpha in normal. denervated and dystrophic human muscle. In muscle biopsies from 12 normal subjects, 16 casts of neurogenic muscular atrophy, 4 ca ses of Duchenne muscular dystrophy, and 4 cases of limb girdle dystrop hy, CNTFR alpha mRNA levels were determined by Northern blotting. Tran script levels were significantly increased in cases of neurogenic atro phy compared to normal controls and dystrophic muscle. By nonradioacti ve in situ hybridization, CNTFR alpha transcripts were detected in the sarcoplasm of both normal sized and atrophic muscle fibers. In additi on, soluble CNTFR alpha was elevated 4.4-fold in the urine of ALS pati ents compared to normal adults. These results suggest that the express ion of CNTFR alpha in human skeletal muscle fibers is regulated by inn ervation. This regulation appears to be selective, because CNTFR alpha mRNA was not increased in dystrophic human muscle. Increased CNTFR al pha could confer higher sensitivity to CNTF during neurodegeneration o r nerve fiber regeneration.