Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats.
BACKGROUND
Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is present and confined to the basal layer.


OBJECTIVE
To examine histological changes in and dynamics of EGF-R expression during healing after acid reflux oesophagitis in a rat model.


METHODS
Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF-R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF-R mRNA and protein by RT-PCR and Western blotting or immunohistochemistry.


RESULTS
Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 +/- 3.09 microm in controls to 142.73 +/- 11.59 microm (P < 0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU-positive cells among basal cells on day 14 was significantly increased from 7.1 +/- 0.8/field in controls to 30.9 +/- 3.0/field in ligated rats. Expression of EGF-R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF-R staining.


CONCLUSIONS
Acid reflux-induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF-R expression. Activation of EGF-R gene and protein in response to acid reflux-induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.
Fujiwara
Y
Y
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Japan. yasu@med.osaka-cu.ac.jp
Higuchi
K
K
Takashima
T
T
Hamaguchi
M
M
Watanabe
T
T
Tominaga
K
K
Oshitani
N
N
Matsumoto
T
T
Arakawa
T
T
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis*; D004942:Esophagitis, Peptic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000473:pathology; D015870:Gene Expression; D008026:Ligation; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D066246:ErbB Receptors