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Effects of lansoprazole on the expression of VEGF and cellular proliferation in a rat model of acetic acid-induced gastric ulcer

  • Original Article—Alimentary Tract
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Abstract

Background

A recent study reported that in addition to their inhibitory effect on gastric acid secretion, some proton pump inhibitors also exert a cytoprotective effect on the gastric mucosa. We investigated the effects of lansoprazole (LPZ) on the epithelial cell cycle, and on the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2).

Methods

We examined the effects of 25 and 5 mg/kg LPZ on ulcer healing in an acetic acid-induced ulcer model in rats with and without indomethacin (IND) treatment. On days 14 and 28 after ulcer formation, we compared the ulcer diameter, bromodeoxyuridine (BrdU) uptake, apoptosis, vascular density, and the expressions of VEGF and MMP-2 in the different groups.

Results

LPZ administration increased the BrdU uptake that was reduced by IND administration. LPZ administration also increased VEGF expression at the ulcer margin in a dose-dependent manner. However, LPZ administration did not increase VEGF expression following IND pretreatment. Administration of IND alone significantly decreased MMP-2 expression at the ulcer margin; on the other hand, subsequent administration of LPZ increased the MMP-2 expression.

Conclusion

One of the mechanisms of ulcer healing brought about by LPZ may be the involvement of endogenous prostaglandin (PG) secretion. The effect of endogenous PG secretion may be related to the induction of VEGF expression. On the other hand, LPZ administration increased MMP-2 expression, and this effect was not influenced by the inhibition of PG synthesis. The mechanisms of LPZ on ulcer healing may be involved by VEGF expression through endogenous PGs secretion. Additionally, the stimulated expression of MMP-2, which is not secreted by endogenous PGs, is another important factor for ulcer healing by LPZ.

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Abbreviations

PPI:

Proton pump inhibitor

LPZ:

Lansoprazole

VEGF:

Vascular endothelial growth factor

MMP:

Matrix metalloproteinase

PG:

Prostaglandin

IND:

Indomethacin

BrdU:

Bromodeoxyuridine

TUNEL:

Terminal uridine deoxynucleotide nick end-labeling

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan

    Shun Kobayashi, Noriko Nakajima, Yoko Ito & Mitsuhiko Moriyama

Authors
  1. Shun Kobayashi
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  2. Noriko Nakajima
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  3. Yoko Ito
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  4. Mitsuhiko Moriyama
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Correspondence to Noriko Nakajima.

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Kobayashi, S., Nakajima, N., Ito, Y. et al. Effects of lansoprazole on the expression of VEGF and cellular proliferation in a rat model of acetic acid-induced gastric ulcer. J Gastroenterol 45, 846–858 (2010). https://doi.org/10.1007/s00535-010-0224-6

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  • DOI: https://doi.org/10.1007/s00535-010-0224-6

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