Expression of insulin growth factor‐1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation

Expression of insulin growth factor‐1 splice variants and structural genes in rabbit skeletal... 1 Skeletal muscle is a major source of circulating insulin growth factor‐1 (IGF‐1), particularly during exercise. It expresses two main isoforms. One of the muscle IGF‐1 isoforms (muscle L.IGF‐1) is similar to the main liver IGF‐1 and presumably has an endocrine action. The other muscle isoform as a result of alternative splicing has a different 3′ exon sequence and is apparently designed for an autocrine/paracrine action (mechano‐growth factor, MGF). Using RNase protection assays with a probe that distinguishes these differently spliced forms of IGF‐1, their expression and also the expression of two structural genes was measured in rabbit extensor digitorum longus muscles subjected to different mechanical signals. 2 Within 4 days, stretch using plaster cast immobilization with the limb in the plantar flexed position resulted in marked upregulation of both forms of IGF‐1 mRNA. Electrical stimulation at 10 Hz combined with stretch (overload) resulted in an even greater increase of both types of IGF‐1 transcript, whereas electrical stimulation alone, i.e. without stretch, resulted in no significant increase over muscle from sham‐operated controls. Previously, it was shown that stretch combined with electrical stimulation of the dorsiflexor muscles in the adult rabbit results in a marked increase in muscle mass involving increases in both length and girth, within a few days. The expression of both systemic and autocrine IGF‐1 growth factors provides a link between the mechanical signal and the marked increase in the structural gene expression involved in tissue remodelling and repair. 3 The expression of the β actin gene was seen to be markedly upregulated in the stretched and stretched/stimulated muscles. It was concluded that the increased expression of this cytoskeletal protein gene is an indication that the production of IGF‐1 may initially be a response to local damage. 4 Switches in muscle fibre phenotype were studied using a specific gene probe for the 2X myosin heavy chain gene. Type 2X expression was found to decrease markedly with stimulation alone and when electrical stimulation was combined with stretch. Unlike the induction of IGF‐1 and β actin, the decreased expression of the 2X myosin mRNA was less marked in the ‘stretch only’ muscles. This indicates that the interconversion of fibre type 2X to 2A may in some situations be commensurate with, but not under the control of IGF‐1. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

Expression of insulin growth factor‐1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation

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Publisher
Wiley
Copyright
Copyright © 1999 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3751
eISSN
1469-7793
DOI
10.1111/j.1469-7793.1999.0583v.x
Publisher site
See Article on Publisher Site

Abstract

1 Skeletal muscle is a major source of circulating insulin growth factor‐1 (IGF‐1), particularly during exercise. It expresses two main isoforms. One of the muscle IGF‐1 isoforms (muscle L.IGF‐1) is similar to the main liver IGF‐1 and presumably has an endocrine action. The other muscle isoform as a result of alternative splicing has a different 3′ exon sequence and is apparently designed for an autocrine/paracrine action (mechano‐growth factor, MGF). Using RNase protection assays with a probe that distinguishes these differently spliced forms of IGF‐1, their expression and also the expression of two structural genes was measured in rabbit extensor digitorum longus muscles subjected to different mechanical signals. 2 Within 4 days, stretch using plaster cast immobilization with the limb in the plantar flexed position resulted in marked upregulation of both forms of IGF‐1 mRNA. Electrical stimulation at 10 Hz combined with stretch (overload) resulted in an even greater increase of both types of IGF‐1 transcript, whereas electrical stimulation alone, i.e. without stretch, resulted in no significant increase over muscle from sham‐operated controls. Previously, it was shown that stretch combined with electrical stimulation of the dorsiflexor muscles in the adult rabbit results in a marked increase in muscle mass involving increases in both length and girth, within a few days. The expression of both systemic and autocrine IGF‐1 growth factors provides a link between the mechanical signal and the marked increase in the structural gene expression involved in tissue remodelling and repair. 3 The expression of the β actin gene was seen to be markedly upregulated in the stretched and stretched/stimulated muscles. It was concluded that the increased expression of this cytoskeletal protein gene is an indication that the production of IGF‐1 may initially be a response to local damage. 4 Switches in muscle fibre phenotype were studied using a specific gene probe for the 2X myosin heavy chain gene. Type 2X expression was found to decrease markedly with stimulation alone and when electrical stimulation was combined with stretch. Unlike the induction of IGF‐1 and β actin, the decreased expression of the 2X myosin mRNA was less marked in the ‘stretch only’ muscles. This indicates that the interconversion of fibre type 2X to 2A may in some situations be commensurate with, but not under the control of IGF‐1.

Journal

The Journal of PhysiologyWiley

Published: Apr 1, 1999

References

  • Activity‐dependent induction of slow myosin gene expression in isolated fast‐twitch mouse muscle
    Barton‐Davis, Barton‐Davis; LaFramoise, LaFramoise; Kushmerick, Kushmerick
  • Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models
    Booth, Booth; Thomason, Thomason
  • Modulation of IGF mRNA abundance during stretch‐induced skeletal muscle hypertrophy and regression
    Czerwinski, Czerwinski; Martin, Martin; Bechtel, Bechtel
  • Muscle growth in response to mechanical stimuli
    Goldspink, Goldspink; Cox, Cox; Smith, Smith; Eavues, Eavues; Osbaldeston, Osbaldeston; Lee, Lee; Mantle, Mantle
  • Cloned glutamate receptors
    Hollmann, Hollmann; Heinemann, Heinemann
  • Iix and slow myosin expression follow mitochondrial increases in transforming muscle fibers
    Jacobs, Jacobs; Ashley, Ashley; Russell, Russell
  • Altered gene expression in fast‐twitch muscle induced by chronic stimulation
    Pette, Pette; Dusterhoft, Dusterhoft
  • The influence of activity on some contractile characteristics of mammalian fast and slow muscles
    Salmons, Salmons; Vrbova, Vrbova
  • Growth, differentiation and survival: Multiple physiological functions for the insulin‐like growth factors
    Stewart, Stewart; Rotwein, Rotwein

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