Role of insulin-like growth factor binding protein (IGFBP)-3 in TGF-beta- and GDF-8 (myostatin)-induced suppression of proliferation in porcine embryonic myogenic cell cultures

J Cell Physiol. 2003 Nov;197(2):225-31. doi: 10.1002/jcp.10362.

Abstract

Both transforming growth factor (TGF-beta) and growth and development factor (GDF)-8 (myostatin) affect muscle differentiation by suppressing proliferation and differentiation of myogenic cells. In contrast, insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of myogenic cells. In vivo, IGFs are found in association with a family of high-affinity insulin-like growth factor binding proteins (IGFBP 1-6) that affect their biological activity. Treatment of porcine embryonic myogenic cell (PEMC) cultures with either TGF-beta(1) or GDF-8 suppressed proliferation and increased production of IGFBP-3 protein and mRNA (P < 0.005). An anti-IGFBP-3 antibody that neutralizes the biological activity of IGFBP-3 reduced the ability of either TGF-beta(1) or GDF-8 to suppress PEMC proliferation (P < 0.005). However, this antibody did not affect proliferation rate in the presence of both TGF-beta(1) and GDF-8. These data show that IGFBP-3 plays a role in mediating the activity of either TGF-beta(1) or GDF-8 alone but not when both TGF-beta(1) and GDF-8 are present. In contrast to findings in T47D breast cancer cells, treatment of PEMC cultures with IGFBP-3 did not result in increased levels of phosphosmad-2. Since TGF-beta and GDF-8 are believed to play a significant role in regulating proliferation and differentiation of myogenic cells, our current data showing that IGFBP-3 plays a role in mediating the activity of these growth factors in muscle cell cultures strongly suggest that IGFBP-3 also may be involved in regulating these processes in myogenic cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Feedback, Physiological / drug effects
  • Feedback, Physiological / physiology
  • Insulin-Like Growth Factor Binding Protein 3 / antagonists & inhibitors
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Myoblasts / cytology
  • Myoblasts / drug effects
  • Myoblasts / metabolism*
  • Myostatin
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Smad2 Protein
  • Sus scrofa
  • Trans-Activators / drug effects
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1

Substances

  • Antibodies
  • DNA-Binding Proteins
  • Insulin-Like Growth Factor Binding Protein 3
  • Myostatin
  • RNA, Messenger
  • Smad2 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1