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


METHODS
An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia.


RESULTS
DCAMKL1 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.


CONCLUSIONS
The 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.
Kikuchi
Miho
M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nagata
Hiroshi
H
Watanabe
Norihito
N
Watanabe
Hiromitsu
H
Tatemichi
Masayuki
M
Hibi
Toshifumi
T
D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D007410:Intestinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000009:adverse effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013270:Stomach / Q000166:cytology / Q000502:physiology*; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000071164:Trefoil Factor-2
D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D008769:Methylnitronitrosoguanidine; D000089742:Doublecortin-Like Kinases; C485526:Dclk1 protein, rat; D017346:Protein Serine-Threonine Kinases; D019342:Acetic Acid