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Volume 130, Issue 4, Pages (April 2006)

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Presentation on theme: "Volume 130, Issue 4, Pages (April 2006)"— Presentation transcript:

1 Volume 130, Issue 4, Pages 1169-1180 (April 2006)
Gastrin Increases Murine Intestinal Crypt Regeneration Following Injury  Penelope D. Ottewell, Carrie A. Duckworth, Andrea Varro, Rod Dimaline, Timothy C. Wang, Alastair J.M. Watson, Graham J. Dockray, D. Mark Pritchard  Gastroenterology  Volume 130, Issue 4, Pages (April 2006) DOI: /j.gastro Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

2 Figure 1 Photomicrographs showing small intestine at low power (A–D), small intestine at high power (E–H), colon at low power (I–L), and colon at high power (M–P) from control FVB/N (A, E, I, M), control INS-GAS (B, F, J, N), FVB/N 96 hours after 12 Gy γ-radiation (C, G, K, O), INS-GAS 96 hours after 12 Gy γ-radiation (D, H, L, P) mice. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

3 Figure 2 Colonic (A) and small intestinal crypt survival (B) 96 hours following 8, 10, 12, or 14 Gy γ-radiation in male wild-type FVB/N (solid line) and INS-GAS (dotted line) mice. Mean ± standard deviation; differences were significant in both tissues at 12 and 14 Gy (P < .05). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

4 Figure 3 Colonic (A) and small intestinal (B) crypt survival and serum amidated gastrin concentrations (C) from wild-type (FVB/N) (black), INS-GAS (grey) and FVB/N treated daily with 75 mg/kg omeprazole (white) mice 96 hours after 14 Gy γ-radiation. Mean ± standard deviation. *P < .05 compared to FVB/N. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

5 Figure 4 Colonic (A) and small intestinal (B) crypt survival from male omeprazole treated FVB/N mice + vehicle (black), omeprazole treated FVB/N mice + YF476 (white), INS-GAS mice + vehicle (grey) and INS-GAS mice + YF476 (white) 96 hours following 14 Gy γ-radiation. Mean ± standard deviation. *P < .05 compared to equivalent mice without YF476. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

6 Figure 5 Percentage of surviving cells per hemicrypt in colon (A) and small intestine (B) 72 and 96 hours following administration of 2× 400 mg/kg 5-FU. (C) Small intestinal crypt survival 96 hours following administration of 2× 400 mg/kg 5-FU from wild-type male FVB/N (black) and INS-GAS (grey) mice. Mean ± standard deviation. *P < .05 compared to FVB/N. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

7 Figure 6 Percent weight change (A), crypt survival in distal colon at days 8 and 11 (B), and serum amidated gastrin concentration at day 8 (C) in FVB/N (black/solid line) and INS-GAS (grey/dotted line) female mice given 3% DSS in the drinking water for 5 days and then allowed to recover. Mean ± standard deviation. *P < .05 compared to FVB/N. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

8 Figure 7 (A) Western blot analysis of CCK-2 receptor and pan-actin expression in small intestinal and colonic epithelium from FVB/N mice in the unirradiated state and at various times following 14 Gy γ-radiation. AGS cells were used as a negative control and AGS cells stably transfected with the CCK-2 receptor (AGS-GR) cells were used as a positive control. Murine samples were pooled from 4 mice per timepoint. (B) Photomicrographs of immunohistochemistry for the CCK-2 receptor in colonic (B and C) and small intestinal (D and E) crypts from FVB/N mice in the resting state (B and D) and 96 hours after 14 Gy γ-radiation (C and E). Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

9 Figure 8 (A) Nested RT-PCR analysis of IEC-6 cells for CCK-2 receptor mRNA and GAPDH mRNA at various times following 4 Gy γ-radiation. St, rat stomach positive control. (B) Western blot analysis of CCK-2 and pan-actin in IEC-6 cells in the untreated state and 24 hours after 4 Gy γ-radiation. (C) Gastrin/receptor binding in IEC-6 cells (expressed as percent of maximum binding after irradiation) 24 hours following exposure to 4 Gy γ-radiation. 125I-labeled G17 competed with nmol “cold” G17 for binding to the CCK-2 receptor (n = 1 in triplicate). (C) 3H-thymidine incorporation (cpm) in unirradiated IEC-6 cells (black) or following exposure to 4 Gy γ-radiation (grey) following 48 hours in serum free media. White bars show cells similarly treated following administration of 10 nmol/L gastrin-17 in serum-free media for 48 hours (n = 4 in triplicate). *P < .05 compared to irradiated cells without addition of gastrin. Gastroenterology  , DOI: ( /j.gastro ) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions


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