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Related Experiment Video

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Time-Dependent Changes in Muscle IGF1-IGFBP5-PAPP System after Sciatic Denervation.

Ana Isabel Martín1, Álvaro Moreno-Rupérez1, Elena Nebot1

  • 1Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Plaza de Ramón y Cajal sn, 28040 Madrid, Spain.

International Journal of Molecular Sciences
|September 28, 2023
PubMed
Summary

Sciatic denervation causes muscle atrophy by altering the IGF-1 system. Early pappalysin (PAPP-A) increase may aid muscle growth, but later decreases, alongside elevated IGFBP-5, contribute to wasting.

Keywords:
IGF-1IGFBP-5pappalysinsskeletal muscle atrophy

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Area of Science:

  • Muscle physiology and molecular biology
  • Skeletal muscle disease mechanisms
  • Endocrinology and growth factor signaling

Background:

  • Denervation-induced muscle atrophy is a significant clinical problem.
  • Insulin-like growth factor 1 (IGF-1) is crucial for muscle growth, but its role in atrophy is unclear.
  • IGF-1 activity is modulated by IGF-1 binding proteins (IGFBPs) and pappalysins (PAPP-A).

Purpose of the Study:

  • To investigate the time-dependent changes in the IGF1-IGFBP5-PAPP system in gastrocnemius muscle following sciatic denervation.
  • To understand the regulatory mechanisms influencing IGF-1 bioavailability during muscle atrophy.

Main Methods:

  • Sciatic denervation model in rodents.
  • Analysis of gastrocnemius muscle tissue at various time points post-denervation.
  • Measurement of IGF-1, IGFBP-5, and PAPP-A expression and activity.
  • Assessment of proteolytic markers.

Main Results:

  • Muscle atrophy and IGF-1 overexpression were evident from day 3 post-denervation.
  • Proteolytic factors and expression of IGFBP-5 and PAPP-A increased early (days 1-3).
  • PAPP-A levels returned to baseline by days 7-14, while IGFBP-5 remained elevated, with the IGFBP-5/PAPP-A ratio correlating with proteolytic markers.

Conclusions:

  • The early rise in PAPP-A may initially support IGF-1's anabolic actions.
  • The subsequent decline in PAPP-A coupled with sustained IGFBP-5 elevation likely exacerbates muscle wasting.
  • The IGF1-IGFBP5-PAPP axis is a critical regulator of muscle mass following denervation.