Regional variability of colonocyte growth and differentiation in the rat

Sato, Masaki; Ahnen, Dennis J.

doi:10.1002/ar.1092330308

Cited by 49 publications

(27 citation statements)

References 11 publications

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“…The caecal region of the large bowel has a spatial distribution similar to that seen in the small intestine, while the rectal region showed the highest levels of apoptosis at the base of the crypt with a more rapid fall off with increasing cell position than was observed in either the caecal or mid-colon region. If the apoptosis in the large bowel is similarly associated with the stem cell population, these observations suggest regional differences in the distribution of stem cells in the large bowel, as has been suggested by previous labelling studies (Kovacs andPotten, 1973: Sato andAhnen, 1992), with stem cells at the very base of the crypt in the mid and rectal regions. but at higher positions in the caecum (perhaps distributed over cell positions 5-10).…”

Section: Cell Position Relabtionshipssupporting

confidence: 68%

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The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine

Potten

Grant²

1998

Br J Cancer

215

144

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Summary Apoptosis is observed in the crypts of the small intestine of healthy animals and man (spontaneous apoptosis). The levels can be dramatically elevated 3-6 h following ionizing radiation exposure. Both the spontaneous and radiation-induced apoptosis in the small intestine crypts are most frequently observed at the positions in the crypt associated with stem cells (about four cell positions from the base of the crypt). The number of apoptotic deaths can be counted in routine histological preparations, but interpretation of the counts is complicated by numerous factors. However, recording the number of cells containing one or more apoptotic fragments in crypt sections provides a good estimate for the absolute number of cell deaths in crypts. Similarities are noted in the frequency and cell positional relationship of radiationinduced apoptosis in the small intestine of various strains of mice and one strain of rat. Apoptosis in the large intestine is generalty lower in frequency than in the small intestine and, for the mid-colonic and rectal regions, has a different cell positional frequency distribution, with the highest apoptotic yield at the crypt base. The caecal colon has a pattem of apoptotic distribution more similar to that in the small intestine. After exposure to 1 Gy ionizing radiation, the maximum apoptotic yield occurs over a period of 3-6 h in the small intestine. There is some unexplained variability in the values between groups of mice and between different mouse strains. After 8 Gy, the yield remains elevated for several days, however a similar maximum yield is still observed at the eariy times. In mouse large intestine and rat small intestine, the yield continues to rise until about 6 Gy in mouse large intestine and until at least 10 Gy in rat small intestine. Spontaneous apoptosis is interpreted as part of the homeostatic mechanism regulating stem cell numbers. About 1.6 cells per crypt are dying at any one time. Following irradiation, there is an apparent relationship between mitotic and apoptotic levels, suggesting that these processes are linked. The dose-response relationship suggests that there are about six apoptosis-susceptible cells in crypts of the small intestine, with about 2-4 of these occurring at cell positions in which there are other more resistant clonogenic cells. In the large intestine, the position of these apoptosis-susceptible cells varies with region, but the numbers are similar.

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Section: Cell Position Relabtionshipssupporting

confidence: 68%

“…the stem cell population; and that the spatial distribution of apoptosis and also stem cells may differ in the different regions of the large bowel, as has been suggested by some DNA labelling experiments (Kovacs andPotten. 1973: Sato andAhnen. 1992).…”

mentioning

confidence: 99%

The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine

Potten

Grant²

1998

Br J Cancer

215

144

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“…The mechanisms of new crypt generation are not understood but are thought to involve budding from pre-existing crypts (fission). rKGF may be targeting a stem cell population capable of not only elongating crypts and increasing goblet cell differentiation, but of generating new crypts as well (44). The relative diminution in enterocytes detected in the small intestine also was observed in the colon of rKGF-treated animals.…”

Section: Resultsmentioning

confidence: 93%

Keratinocyte growth factor induces proliferation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract.

Housley

Morris²,

Boyle³

et al. 1994

J. Clin. Invest.

261

200

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Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family, was identified as a specific keratinocyte mitogen after isolation from a lung fibroblast line. Recently, recombinant (r)KGF was found to influence proliferation and differentiation patterns of multiple epithelial cell lineages within skin, lung, and the reproductive tract. In the present study, we designed experiments to identify additional target tissues, and focused on the rat gastrointestinal (GI) system, since a putative receptor, K-sam, was originally identified in a gastric carcinoma. Expression of KGF receptor and KGF mRNA was detected within the entire GI tract, suggesting the gut both synthesized and responded to KGF. Therefore, rKGF was administered to adult rats and was found to induce markedly increased proliferation of epithelial cells from the foregut to the colon, and of hepatocytes, one day after systemic treatment. Daily treatment resulted in the marked selective induction of mucin-producing cell lineages throughout the GI tract in a dose-dependent fashion. Other cell lineages were either unaffected (e.g., Paneth cells), or relatively decreased (e.g., parietal cells, enterocytes) in rKGF-treated rats. The direct effect of rKGF was confirmed by demonstrating markedly increased carcinoembryonic antigen production in a human colon carcinoma cell line, LIM1899. Serum levels of albumin were specifically and significantly elevated after daily treatment. These results demonstrate rKIGF can induce epithelial cell activation throughout the GI tract and liver. Further, endogenous KGF may be a normal paracrine mediator of growth within the gut. (J. Clin. Iptvqst. 1994Iptvqst. . 94:1764Iptvqst. -1777

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“…The existence of a proliferation gradient among the different regions of the colon is still controversial (2). In rats, the location of the proliferative zone in the crypt varies between the proximal and the distal colon (49). In our system, we propose that the distal colon relies more heavily on the TGF-h signaling pathway for growth control than does the proximal colon and that alterations in this pathway secondary to Smad3 knockout predispose the distal colon toward neoplasia by creating a state of imbalance between epithelial cell proliferation and cell death by apoptosis and other routes.…”

Section: Apcmentioning

confidence: 99%

Smad3 Deficiency Promotes Tumorigenesis in the Distal Colon of ApcMin/+ Mice

Sodir

Chen²,

Park³

et al. 2006

Cancer Research

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Colorectal cancer, one of the most common human malignancies in the Western world, is often subdivided based on tumor location in either the distal or proximal colon. Several mouse models have been developed to study human colorectal cancer, but few display this clear distinction between the two colonic locations. By crossing Apc Min/+ and Smad3 mutant mice, we showed that combined activation of the Wnt pathway and attenuation of the transforming growth factor-B (TGF-B) pathway causes high multiplicity and rapid onset of invasive tumorigenesis almost exclusively in the distal colon, closely mimicking the familial adenomatous polyposis (FAP) disease and consisting with distinct colorectal cancer etiologies based on tumor location. Transcriptional profiling revealed higher expression of several TGF-B activators in the normal distal mucosa than in proximal mucosa, suggesting a stronger reliance on TGF-B-mediated growth control in the distal than in the proximal colon. ApcÀ/À mice provide an alternative model to Apc Min/+ mice to study FAP and distal sporadic colorectal cancer. This model will be useful in dissecting mechanistic and etiologic differences between proximal and distal colonic cancer, whereas the confinement of tumorigenesis to the distal colon offers unique advantages in monitoring tumor progression by in vivo imaging. (Cancer Res 2006; 66(17): 8430-8)

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Regional variability of colonocyte growth and differentiation in the rat

Cited by 49 publications

References 11 publications

The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine

The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine

Keratinocyte growth factor induces proliferation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract.

Smad3 Deficiency Promotes Tumorigenesis in the Distal Colon of ApcMin/+ Mice

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