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Expression of angiotensin II type 1 and type 2 receptor mRNAs in the gastric mucosa of Helicobacter pylori-infected Mongolian gerbils

  • Original Article—Alimentary Tract
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Abstract

Background

The renin–angiotensin system (RAS) plays an important role in normal homeostasis, carcinogenesis-related angiogenesis, and cell proliferation. Helicobacter pylori infection causes infiltration of inflammatory cells into the gastric mucosa and is considered the major cause of gastric cancer. Whether RAS plays a role in H. pylori infection-related gastric diseases remains unclear. We investigated the changes in gastric mucosal angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) mRNA levels throughout the time course of H. pylori infection in Mongolian gerbils.

Methods

Mongolian gerbils were infected with wild-type H. pylori (for 12 months) or with its isogenic oipA mutant (for 3 months). Gastric mucosal AT1R and AT2R mRNA levels were assessed using real-time reverse transcription-polymerase chain reaction.

Results

The gastric mucosal AT1R mRNA level was significantly associated with the severity of inflammatory cell infiltration into the gastric mucosa that reached maximal levels at 12 months after infection in both the antrum and body. Inflammatory cell infiltration scores and AT1R and AT2R mRNA levels were significantly lower in oipA mutant than wild-type infections. Mucosal AT1R and AT2R mRNA expressions in wild-type H. pylori-infected gerbils with gastric ulcers were significantly higher than in those without ulcers (P < 0.01).

Conclusions

Gastric mucosal ATR expression gradually increases during the course of H. pylori infection. Up-regulation of the RAS in association with progressive gastric inflammation suggests a potential role of the RAS in gastric carcinogenesis. OipA appears to play a role in AT1R and AT2R expression and the resulting inflammation.

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Abbreviations

ACE:

Angiotensin-I converting enzyme

ARB:

AT1R blocker

ATR:

Angiotensin II receptor

AT1R:

Angiotensin II type 1 receptor

AT2R:

Angiotensin II type 2 receptor

CMA:

Chymase

COX:

Cyclooxygenase

FBS:

Fetal bovine serum

MNC:

Mononuclear cell

OipA:

Outer inflammatory protein

PMN:

Polymorphonuclear cell

RAS:

Renin–angiotensin system

RT-PCR:

Real-time reverse transcription-polymerase chain reaction

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Acknowledgments

We acknowledge receipt of the Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grant DK56338, which funds the Texas Medical Center Digestive Diseases Center, and the National Institutes of Health (NIH) grant DK 62813.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA

    Mitsushige Sugimoto, Tomoyuki Ohno & Yoshio Yamaoka

  2. Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan

    Yoshio Yamaoka

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  1. Mitsushige Sugimoto
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  2. Tomoyuki Ohno
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Correspondence to Yoshio Yamaoka.

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Sugimoto, M., Ohno, T. & Yamaoka, Y. Expression of angiotensin II type 1 and type 2 receptor mRNAs in the gastric mucosa of Helicobacter pylori-infected Mongolian gerbils. J Gastroenterol 46, 1177–1186 (2011). https://doi.org/10.1007/s00535-011-0433-7

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  • DOI: https://doi.org/10.1007/s00535-011-0433-7

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