The gastric
hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of
body weight. So far,
ghrelin has mainly been examined as a serological marker for
gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion.
Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of
ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in
ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune
gastritis showed interesting remodeling effects in terms of
ghrelin expression within neuroendocrine cell
hyperplasia by immunohistochemistry. Using confocal
laser microscopy, the
gastrin/
cholecystokinin receptor (CCKB) could be detected on normal
ghrelin cells as well as in autoimmune
gastritis. Functionally, we found evidence for a physiological interaction between
gastrin and
ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic
gastrin levels due to long-term autoimmune
gastritis or short-term
proton pump inhibitor treatment with slightly reactive plasma
gastrin elevations. Total
ghrelin plasma levels showed a significantly inverse correlation with
gastrin under long-term conditions. Autoimmune
gastritis as a relevant condition within gastric
carcinogenesis therefore has two effects on
ghrelin-positive cells due to hypergastrinemia. On the one hand,
gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell
hyperplasia, while on the other hand, plasma
ghrelin is reduced by
gastrin and lost in pseudopyloric and intestinal metaplastic areas.
Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric
carcinogenesis, if altered under these pre neoplastic conditions.