Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis.
OBJECTIVE
A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue.


METHODS
Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale.


RESULTS
Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients.


CONCLUSIONS
TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.
Baughman
R P
RP
Department of Internal Medicine, University of Cincinnati Medical Center, OH 45267-0564, USA. bob.baughman@uc.edu
Lower
E E
EE
Miller
M A
MA
Bejarano
P A
PA
Heffelfinger
S C
SC
D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000032:analysis* / Q000096:biosynthesis
D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors