Altered expression of a putative progenitor cell marker DCAMKL1 in the rat gastric mucosa in regeneration, metaplasia and dysplasia

Abstract

BackgroundDoublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1) is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions.MethodsAn immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia.ResultsDCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2)/spasmolytic polypeptide-expressing metaplasia (SPEM) emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM.ConclusionThe ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic, metaplastic and dysplastic cells, and the progenitor zone shifts according to the pathological circumstances.

The Hyaluronic Acid Receptor CD44 Coordinates Normal and Metaplastic Gastric Epithelial Progenitor Cell Proliferation

“…LGR5 (19), LRIG1 (20), BMI (21)) and even in the more distal gastric antrum (19,22). A handful of molecular pathways and markers (23)(24)(25) have been proposed for the gastric epithelium, but no mechanistic studies revealing molecules that regulate proliferation of the canonical isthmal stem cell either under normal conditions or in response to injury have been reported (4). Furthermore, the mechanisms underlying altered patterns of stem cell behavior during precancerous conditions in any tissue are only beginning to be explored.…”

DCLK1 expression in gastrointestinal stem cells and neoplasia

“…Gastric DCLK1 cells express parietal cell markers and partially co-express MSI1. In rodent models of acute gastritis and of chronic ulcer DCLK1 cells expand beyond the stem cell zone but remain PCNA negative [33,34]. In these conditions as well as after irradiation, DCLK1 cells are found adjacent to the PCNA positive compartment, suggesting a possible role in the restitution of mucosal integrity [33,34].…”

“…In the stomach, DCLK1 cells are found in the stem cell zone located at the isthmus of the fundic glands [33] and are clearly distinct from TFF2 transcript-expressing cells, which are considered the progenitor cells for mucus neck, parietal and zymogenic cells [12,34]. Gastric DCLK1 cells express parietal cell markers and partially co-express MSI1.…”

Histopathological Investigation of the Stomach of Rats Fed a 60% Genetically Modified Corn Diet

“…This type of change to the staining properties of the epithelial cells could indicate the presence of immature cells that had migrated from the proliferative zone. Injury can alter the differentiation of cells from the proliferative zone, that is, it can change stomach cell lineages [78] and thus alter the staining-properties of the gastric gland cells. Non-steroidal anti-inflammatory drugs, ethanol and Helicobacter pylori infection have been known to cause damage/changes to the stomach proliferative zone and consequently initiate the migration of immature cells [78].…”

“…Injury can alter the differentiation of cells from the proliferative zone, that is, it can change stomach cell lineages [78] and thus alter the staining-properties of the gastric gland cells. Non-steroidal anti-inflammatory drugs, ethanol and Helicobacter pylori infection have been known to cause damage/changes to the stomach proliferative zone and consequently initiate the migration of immature cells [78]. The method of regeneration following such damage is still poorly understood, however immunohistochemistry for certain progenitor cell markers and metaplasia can better reveal the nature of the change.…”