Cell

Cell

Volume 76, Issue 3, 11 February 1994, Pages 493-504
Journal home page for Cell

Article
Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle

https://doi.org/10.1016/0092-8674(94)90113-9Get rights and content

Abstract

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, CNTFRα, is expressed by skeletal muscle. Here we show that the other CNTF receptor components, LIFRβ 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.

References (69)

  • B. Friedman et al.

    Regulation of CNTF expression in myelin-related Schwann cells in vivo

    Neuron

    (1992)
  • D.J. Glass et al.

    TrkB mediates BDNFNT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor

    Cell

    (1991)
  • M.A. Hill et al.

    Motoneuron survival activity in extracts of denervated muscle reduced by prior stimulation of the muscle

    Dev. Brain Res.

    (1986)
  • N.Y. Ip et al.

    CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal-transducing receptor component gp130

    Cell

    (1992)
  • N.Y. Ip et al.

    The α component of the CNTF receptor is required for signaling and defines potential CNTF targets in the adult and during development

    Neuron

    (1993)
  • D.J. Johnson et al.

    Exercise-induced changes of biochemical, histochemical and contractile properties of muscle in cordotomized kittens

    Exp. Neurol.

    (1982)
  • M. Manthorpe et al.

    Purification of adult rat sciatic ciliary neuronotrophic factor

    Brain Res.

    (1986)
  • J.-C. Martinou et al.

    Cholinergic differentiation factor (CDFLIF) promotes survival of isolated rat embryonic motoneurons in vitro

    Neuron

    (1992)
  • A. Messing et al.

    Po promoter directs expression of reporter and toxin genes to Schwann cells of transgenic mice

    Neuron

    (1992)
  • D.A. Riley et al.

    The effects of inactivity, programmed stimulation, and denervation on the histochemistry of skeletal muscle fiber types

    Exp. Neurol.

    (1973)
  • N. Stahl et al.

    Cross-linking identifies leukemia inhibitory factor-binding protein as a ciliary neurotrophic factor receptor component

    J. Biol. Chem.

    (1993)
  • H. Thoenen

    The changing scene of neurotrophic factors

    Trends Neurosci.

    (1991)
  • O. Uchitel et al.

    On the appearance of acetylcholine receptors in denervated rat diaphragm, and its dependence on nerve stump length

    Brain Res.

    (1978)
  • L.R. Williams et al.

    High ciliary neuronotrophic specific activity in rat peripheral nerve

    Int. J. Dev. Neurosci.

    (1984)
  • R. Adler et al.

    Cholinergic neuronotrophic factors: intraocular distribution of soluble trophic activity for ciliary neurons

    Science

    (1979)
  • L. Aloe et al.

    Light and electron microscopic studies of the excess growth of sympathetic ganglia in rats injected daily from birth with 6-OHDA and NGF

    Arch. Ital. Biol.

    (1975)
  • Y. Arakawa et al.

    Survival effects of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines

    J. Neurosci.

    (1990)
  • G. Barbin et al.

    Purification of the chick eye ciliary neurotrophic factor

    J. Neurochem.

    (1984)
  • S. Brimijoin

    Trophic roles of axoplasmic transport

  • N.E. Cameron et al.

    Muscle and nerve dysfunction in rats with experimental galactosemia

    Exp. Physiol.

    (1992)
  • B. Davey et al.

    Effect of nerve stump length on cholinesterase in denervated rat diaphragm

    Exp. Neurol.

    (1978)
  • S. Davis et al.

    The receptor for ciliary neurotrophic factor

    Science

    (1991)
  • S. Davis et al.

    Released form of CNTF receptor α component as a soluble mediator of CNTF responses

    Science

    (1993)
  • S. Davis et al.

    LIFRβ and gp 130 as heterodimerizing signal transducers of the tripartite CNTF receptor

    Science

    (1993)

    • Cited by (0)

    †

    Present Address: Alexion Pharmaceuticals, Incorporated, 25 Science Park, Suite 360, New Haven, Connecticut 06511

    View full text
    Copyright © 1994