Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats

Am J Respir Cell Mol Biol. 1994 Nov;11(5):540-51. doi: 10.1165/ajrcmb.11.5.7524566.


To investigate the potential role of transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGF-R) in the fibroproliferative response to acute lung injury, we determined lung steady-state TGF-alpha and EGF-R mRNA levels, TGF-alpha protein levels, and the distribution of TGF-alpha and EGF-R immunoreactive protein of bleomycin-injured and control rat lungs. At 2 and 4 days after a single intratracheal injection of bleomycin, TGF-alpha mRNA levels increased to 159% and 184% of control values, respectively. EGF-R mRNA levels increased to 163%, 314%, and 170% of control values at 1, 7, and 14 days after bleomycin instillation. TGF-alpha protein levels in whole lung extracts increased to 230% of control values at 4 days after bleomycin administration. TGF-alpha and EGF-R immunoreactivity was detected in macrophages, alveolar septal cells, and airway epithelium of control and bleomycin-injured animals with an apparent increase in the intensity and number of specifically immunostained cells following lung injury. TGF-alpha and EGF-R immunoreactive proteins were detected in foci of cellular proliferation and in areas of intraalveolar fibrosis. We conclude that TGF-alpha and the EGF-R are present in normal and bleomycin-injured rat lung and that the expression of this growth factor and its receptor are up-regulated following lung injury. These results suggest that increased expression of TGF-alpha and the EGF-R may be an important mechanism that modulates the fibroproliferative response to acute lung injury.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Base Sequence
  • Bleomycin / administration & dosage
  • Cell Division
  • ErbB Receptors / analysis
  • ErbB Receptors / biosynthesis*
  • Lung / drug effects
  • Lung / immunology
  • Lung / metabolism*
  • Lung / pathology
  • Macrophages, Alveolar / chemistry
  • Male
  • Molecular Sequence Data
  • Proliferating Cell Nuclear Antigen / analysis
  • Pulmonary Alveoli / chemistry
  • Pulmonary Alveoli / cytology
  • Pulmonary Fibrosis / metabolism
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / immunology
  • Respiratory Distress Syndrome / metabolism*
  • Specific Pathogen-Free Organisms
  • Transforming Growth Factor alpha / analysis
  • Transforming Growth Factor alpha / biosynthesis*


  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Transforming Growth Factor alpha
  • Bleomycin
  • ErbB Receptors