Altered Expression of a Putative Progenitor Cell Marker DCAMKL1 in the Rat Gastric Mucosa in Regeneration, Metaplasia and Dysplasia

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2010 Jun 23

PMID 20565818

Citations 19

Authors

Miho Kikuchi

Hiroshi Nagata

Norihito Watanabe

Hiromitsu Watanabe

Masayuki Tatemichi

Toshifumi Hibi

Affiliations

Soon will be listed here.

Abstract

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.

Conclusion: 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.

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References

Yatabe Y, Tavare S, Shibata D . Investigating stem cells in human colon by using methylation patterns. Proc Natl Acad Sci U S A. 2001; 98(19):10839-44. PMC: 58561. DOI: 10.1073/pnas.191225998. View

Willems G, Vansteenkiste Y, Smets P . Effects of ethanol on the cell proliferation kinetics in the fundic mucosa of dogs. Am J Dig Dis. 1971; 16(12):1057-63. DOI: 10.1007/BF02235160. View

Qiao X, Ziel J, McKimpson W, Madison B, Todisco A, Merchant J . Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology. 2007; 133(6):1989-98. PMC: 2329573. DOI: 10.1053/j.gastro.2007.09.031. View

Hansen O, Pedersen T, Larsen J . A method to study cell proliferation kinetics in human gastric mucosa. Gut. 1975; 16(1):23-7. PMC: 1410934. DOI: 10.1136/gut.16.1.23. View

Samuel S, Walsh R, Webb J, Robins A, Potten C, Mahida Y . Characterization of putative stem cells in isolated human colonic crypt epithelial cells and their interactions with myofibroblasts. Am J Physiol Cell Physiol. 2008; 296(2):C296-305. PMC: 2643851. DOI: 10.1152/ajpcell.00383.2008. View

Nomura S, Baxter T, Yamaguchi H, Leys C, Vartapetian A, Fox J . Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice. Gastroenterology. 2004; 127(2):582-94. DOI: 10.1053/j.gastro.2004.05.029. View

Poulsen S, Thulesen J, Hartmann B, Kissow H, Nexo E, Thim L . Injected TFF1 and TFF3 bind to TFF2-immunoreactive cells in the gastrointestinal tract in rats. Regul Pept. 2003; 115(2):91-9. DOI: 10.1016/s0167-0115(03)00145-9. View

Nozaki K, Ogawa M, Williams J, LaFleur B, Ng V, Drapkin R . A molecular signature of gastric metaplasia arising in response to acute parietal cell loss. Gastroenterology. 2008; 134(2):511-22. PMC: 2857727. DOI: 10.1053/j.gastro.2007.11.058. View

Sureban S, May R, Ramalingam S, Subramaniam D, Natarajan G, Anant S . Selective blockade of DCAMKL-1 results in tumor growth arrest by a Let-7a MicroRNA-dependent mechanism. Gastroenterology. 2009; 137(2):649-59, 659.e1-2. PMC: 2775069. DOI: 10.1053/j.gastro.2009.05.004. View

10.

Nagata H, Akiba Y, Suzuki H, Okano H, Hibi T . Expression of Musashi-1 in the rat stomach and changes during mucosal injury and restitution. FEBS Lett. 2005; 580(1):27-33. DOI: 10.1016/j.febslet.2005.11.041. View

11.

Yamaguchi H, Goldenring J, Kaminishi M, Lee J . Association of spasmolytic polypeptide-expressing metaplasia with carcinogen administration and oxyntic atrophy in rats. Lab Invest. 2002; 82(8):1045-52. DOI: 10.1097/01.lab.0000022225.45996.21. View

12.

Barker N, Huch M, Kujala P, van de Wetering M, Snippert H, van Es J . Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell. 2010; 6(1):25-36. DOI: 10.1016/j.stem.2009.11.013. View

13.

Houghton J, Stoicov C, Nomura S, Rogers A, Carlson J, Li H . Gastric cancer originating from bone marrow-derived cells. Science. 2004; 306(5701):1568-71. DOI: 10.1126/science.1099513. View

14.

Poulsen S, Thulesen J, Christensen L, Nexo E, Thim L . Metabolism of oral trefoil factor 2 (TFF2) and the effect of oral and parenteral TFF2 on gastric and duodenal ulcer healing in the rat. Gut. 1999; 45(4):516-22. PMC: 1727673. DOI: 10.1136/gut.45.4.516. View

15.

Sakamoto H, Yoshimura K, Saeki N, Katai H, Shimoda T, Matsuno Y . Genetic variation in PSCA is associated with susceptibility to diffuse-type gastric cancer. Nat Genet. 2008; 40(6):730-40. DOI: 10.1038/ng.152. View

16.

Watanabe H, Ito A . Relationship between gastric tumorigenesis and intestinal metaplasia in rats given x-radiation and/or N-methyl-N'-nitro-N-nitrosoguanidine. J Natl Cancer Inst. 1986; 76(5):865-70. View

17.

Kirchner T, Muller S, Hattori T, Mukaisyo K, Papadopoulos T, Brabletz T . Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis. Virchows Arch. 2001; 439(4):512-22. DOI: 10.1007/s004280100477. View

18.

Zhang Y, Huang X . Investigation of doublecortin and calcium/calmodulin-dependent protein kinase-like-1-expressing cells in the mouse stomach. J Gastroenterol Hepatol. 2010; 25(3):576-82. DOI: 10.1111/j.1440-1746.2009.06114.x. View

19.

Yeomans N, Skeljo M . Repair and healing of established gastric mucosal injury. J Clin Gastroenterol. 1991; 13 Suppl 1:S37-41. DOI: 10.1097/00004836-199112001-00006. View

20.

Schmidt P, Lee J, Joshi V, Playford R, Poulsom R, Wright N . Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab Invest. 1999; 79(6):639-46. View