Trefoil Factors Are Expressed in Human and Rat Endocrine Pancreas: Differential Regulation by Growth Hormone

Abstract

Trefoil factors (TFFs) 1, 2, and 3 are expressed in mucosal epithelia. TFFs are particular abundant in the intestine in which they play a crucial role in maintenance and restitution of the epithelium. Because pancreas developmentally arises from the primitive foregut, we explored the expression of TFFs in the pancreas in man and rat. Immunocytochemical staining of adult human pancreas showed abundant TFF3 immunoreactivity in pancreatic islets and some duct cells, whereas weak TFF1 and no TFF2 staining were detected. In the islets TFF3 localized to most insulin and some glucagon and pancreatic polypeptide-producing cells. TFF3 immunoreactivity was colocalized with insulin and glucagon in distinct cell clusters in human fetal pancreas at wk 14 and in the newborn rat pancreas. In isolated human and rat islets, TFF3 and TFF1 mRNA was identified by RT-PCR, and TFF3 protein was detected in human pancreas and islets by ELISA. Exposure of neonatal rat islets or insulinoma cells to GH, a known beta-cell growth factor, resulted in markedly increased TFF3 but decreased TFF1 mRNA levels. The effect of GH on TFF3 expression was confirmed by Western blot. Culture of neonatal rat islets in the presence of TFF3 resulted in attachment and migration of the islet cells, but no effects on proliferation, insulin secretion or cytokine-induced apoptosis were seen. These data demonstrate expression of TFFs in the endocrine pancreas, but their possible functions remain unknown.

Trefoil factor-3 expression in human colon cancer liver metastasis

“…Curiously, we noted rather strong expression of TFF3 in one specimen of metastatic colon cancer that demonstrated endocrine-like differentiation. TFF3 expression has been reported in pancreatic islet cells, co-localizing with insulin and glucagons, with expression increasing in response to growth hormone in vitro [41].…”

The trefoil factor family – small peptides with multiple functionalities

“…However, pancreatic expression of all TFFs has been noted in rodents and man [5,15,21,39,52,60,61], mainly in the pancreatic ducts, while one group also reports the expression of TFF3 in the endocrine pancreas [62].…”

Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

“…At a much later stage, the exocrine progenitors are responsible for the differentiation and expansion of the exocrine acinar epithelium, which is mainly a late fetal or early perinatal event. Figure 1B shows a section of the ductal system from a 14-week-old fetus (Jackerott et al, 2006) with initial endocrine progenitors budded from the ductal epithelium, and Figure 1C shows a section from an 18-week-old fetus with endocrine progenitors budded from the ductal epithelium as well as acinar progenitors surrounding the ductal epithelium.…”