Developmental expression of transforming growth factor-? and epidermal growth factor receptor proteins in the human pancreas and digestive tract

Abstract

This study was designed to localize transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) expression in the developing human gastrointestinal tract and pancreas. Immunohistochemical techniques using specific antibodies against human TGF-alpha and EGFR were performed on digestive tissues of fetuses from 9 to 10 to 24 weeks of gestation, children and adults. In fetuses, TGF-alpha and EGFR proteins were expressed in all epithelial tissues studied with a good correlation and from an age as early as 9 to 10 weeks of gestation, except for TGF-alpha in the esophagus. The strongest TGF-alpha immunostaining was noted in the stomach and the proximal colon. Unexpectedly, immunoreactive gut endocrine cells were observed with the two antibodies used. Relatively numerous in fetuses, they decreased in number with age and were rare in adults particularly along the colon. Enteroglucagonsecreting cells were shown to express TGF-alpha, while some gastrin, somatostatin and pancreatic glucagon cells were immunostained with EGFR antibodies. The presence of TGF-alpha and its receptor in digestive tract epithelium and pancreatic tissues early in fetal life suggests a functional role for TGF-alpha during the developmental process of the digestive system. We demonstrate that TGF-alpha is also produced by endocrine cells and might have an additional mode of action other than paracrine, at least during fetal life.

MUC5AC, a Gel-Forming Mucin Accumulating in Gallstone Disease, Is Overproduced via an Epidermal Growth Factor Receptor Pathway in the Human Gallbladder

“…In a previous study, Lee et al 45 described EGF-R immunoreactivity in chronic cholecystitis as weak to moderate, but this was in reference to a higher expression in gallbladder carcinoma, and the conditions of detection in this study compared with ours were likely less sensitive (eg, primary antibody used at a dilution of 1:1500 instead of 1:100). The fact that EGF-R immunoreactivity was detected in the apical domain of epithelial cells was also previously reported in the gastrointestinal tract 46,47 and in the airways, 48 other sites of mucin production. In the gallbladder epithelium, this finding was consistent with activation of the EGF-R pathway by luminal factors (ie, EGF and TGF-␣ that are present in bile).…”

Expression of gastrin and transforming growth factor-α during duct to islet cell differentiation in the pancreas of duct-ligated adult rats

“…In particular, TGFa has been implicated in the proliferation of gastric mucosal cell types [40,41]. In the pancreas, TGFa, like gastrin, is also expressed in the late fetal period, but, contrary to gastrin, continues to be present after birth [42]. During this period TGFa immunoreactivity is mainly found in islet and duct cells.…”

Association between Endocrine Pancreas and Ductal System. More than an Epiphenomenon of Endocrine Differentiation and Development?

“…Its receptor (EGF-R) is broadly expressed in the pancreas, but mostly by islet cells (Hormy and Lehy 1994). TGF-␣ is detectable in ducts of normal rat pancreas (Wang et al 1997a) and is overexpressed by duct and acinar cells in chronic pancreatitis (Korc et al 1994).…”