Chronic stress augments esophageal inflammation, and alters the expression of transient receptor potential vanilloid 1 and protease‑activated receptor 2 in a murine model

Wulamu,Wubulikasimu; Yisireyili,Maimaiti; Aili,Aikebaier; Takeshita,Kyosuke; Alimujiang,Aziguli; Aipire,Aliyeguli; Li,Yiliang; Jiang,Yuan; Aizezi,Maimaitiaili; Li,Zanlin; Abudureyimu,Kelimu

doi:10.3892/mmr.2019.10192

Chronic stress augments esophageal inflammation, and alters the expression of transient receptor potential vanilloid 1 and protease‑activated receptor 2 in a murine model

Authors:
- Wubulikasimu Wulamu
- Maimaiti Yisireyili
- Aikebaier Aili
- Kyosuke Takeshita
- Aziguli Alimujiang
- Aliyeguli Aipire
- Yiliang Li
- Yuan Jiang
- Maimaitiaili Aizezi
- Zanlin Li
- Kelimu Abudureyimu
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Affiliations: Research Institute of General and Minimally Invasive Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China, Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 460‑8550, Japan, Department of Obstetrics and Gynecology Clinic, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China, Department of Minimally Invasive Surgery, Hernia and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China, Department of Cardiac Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China
Published online on: April 25, 2019 https://doi.org/10.3892/mmr.2019.10192
Pages: 5386-5396

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Abstract

Stress is a pivotal factor for inflammation, reactive oxygen species (ROS) production and formation of visceral hypersensitivity (VH) in the process of gastroesophageal reflux disease (GERD). In the present study, the effects of stress on esophageal inflammation, oxidative stress and VH were investigated in a chronic restraint stress mouse model. C57BL/6J male mice were subjected to 2 weeks of intermittent restraint stress, and histopathological analysis revealed that stress induced esophageal inflammation and fibrosis, while no distinct changes were detected in non‑stressed control mice. In addition, increased NADPH oxidase 4 expression was observed in the plasma and esophagus of stressed mice, indicating accumulation of ROS. The expression levels of antioxidants, including Mn‑superoxide dismutase (MnSOD), Cu/Zn‑SOD, catalase and glutathione peroxidase, were also analyzed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, transient receptor potential vanilloid 1 (TRPV‑1) and protease‑activated receptor 2 (PAR‑2), which are crucial receptors for VH, were measured by immunohistochemistry and RT‑qPCR. The results demonstrated that stress markedly reduced antioxidant expression, while it significantly upregulated TRPV‑1 and PAR‑2 expression levels in the mouse esophagus. Finally, 2 weeks of restraint stress significantly increased the esophageal and plasma levels of inflammatory cytokines, including interleukin (IL)‑6, IL‑8, interferon‑γ and tumor necrosis factor‑α. Taken together, the present study results indicated that stress‑induced esophageal inflammation and ROS generation involves VH.

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