Expression of transforming growth factor-alpha and epidermal growth factor receptor is increased following bleomycin-induced lung injury in rats.
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.
Madtes
D K
DK
Fred Hutchinson Cancer Research Center, Department of Medicine, University of Washington, Seattle.
Busby
H K
HK
Strandjord
T P
TP
Clark
J G
JG
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D001761:Bleomycin / Q000008:administration & dosage; D002455:Cell Division; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000166:cytology; D011658:Pulmonary Fibrosis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000096:biosynthesis*
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D001761:Bleomycin; D066246:ErbB Receptors