TGF-beta 1 modulates human airway smooth-muscle cell proliferation induced by mitogens

Am J Respir Cell Mol Biol. 1997 Jan;16(1):85-90. doi: 10.1165/ajrcmb.16.1.8998083.


Asthma is a disease of airway inflammation and bronchoconstriction that results in airway smooth-muscle cell hypertrophy and hyperplasia. The underlying mechanisms that induce myocyte proliferation remain unknown. Evidence suggests that cytokines such as transforming growth factor (TGF)-beta 1 may play a role in modulating this process. In this study, we examined the effects of TGF-beta 1 on human airway smooth-muscle (HASM) cell proliferation. We found that treatment of HASM cells with TGF-beta 1 inhibited epidermal growth factor (EGF)- and thrombin-induced DNA synthesis. This inhibition was both dose and time dependent. We then investigated whether these effects are mediated through activation of mitogen-activated protein kinase (MAP kinase), an enzyme that is thought to play a central role in the regulation of cell proliferation. We found that MAP kinase activation induced by EGF was not modulated by TGF-beta 1, despite TGF-beta 1 inhibiting EGF-induced HASM cell growth. These data suggest that TGF-beta 1 inhibits mitogen-induced HASM cell proliferation, but does so downstream from MAP kinase activation, or via a parallel pathway that is independent of MAP kinase activation.

Publication types

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

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Division / drug effects
  • Cells, Cultured
  • DNA / biosynthesis
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology
  • Humans
  • Mitogens / pharmacology*
  • Muscle, Smooth / cytology*
  • Muscle, Smooth / drug effects
  • Thrombin / pharmacology
  • Trachea / cytology*
  • Trachea / drug effects
  • Transforming Growth Factor beta / pharmacology*


  • Mitogens
  • Transforming Growth Factor beta
  • Epidermal Growth Factor
  • DNA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Thrombin