IGFBP-3 mediates TGF-beta1-induced cell growth in human airway smooth muscle cells

Am J Physiol Lung Cell Mol Physiol. 2000 Mar;278(3):L545-51. doi: 10.1152/ajplung.2000.278.3.L545.

Abstract

Both insulin-like growth factor binding protein-3 (IGFBP-3) and transforming growth factor-beta (TGF-beta) have been separately shown to have cell-specific growth-inhibiting or growth-potentiating effects. TGF-beta stimulates IGFBP-3 mRNA and peptide expression in several cell types, and TGF-beta-induced growth inhibition and apoptosis have been shown to be mediated through the induction of IGFBP-3. However, a link between the growth stimulatory effects of TGF-beta and IGFBP-3-induction has not been shown. In this study, we investigated the role of IGFBP-3 in mediating TGF-beta1-induced cell growth using human airway smooth muscle (ASM) cells as our model. TGF-beta1 (1 ng/ml) treatment induced a 10- to 20-fold increase in the levels of expression of IGFBP-3 mRNA and protein. Addition of either IGFBP-3 or TGF-beta1 to the growth medium resulted in an approximately twofold increase in cell proliferation. Coincubation of ASM cells with IGFBP-3 antisense (but not sense) oligomers as well as with an IGFBP-3 neutralizing antibody (but not with control IgG) blocked the growth induced by TGF-beta1 (P < 0.001). Several IGFBP-3-associated proteins were observed in ASM cell lysates, which may have a role in the cellular responses to IGFBP-3. These findings demonstrate that IGFBP-3 is capable of mediating the growth stimulatory effect of TGF-beta in ASM cells.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Bronchi / cytology*
  • Bronchi / metabolism
  • Cell Division / drug effects
  • Cell Division / physiology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / pharmacology
  • Insulin-Like Growth Factor Binding Protein 3 / physiology*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Male
  • Muscle, Smooth / cytology*
  • Muscle, Smooth / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptors, Cell Surface
  • Transforming Growth Factor beta