Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

Zhu,He; Xiao,Xi; Shi,Yuying; Wu,Yingxiu; Huang,Yusheng; Li,Detang; Xiong,Fen; He,Guodong; Chai,Yuna; Tang,Hongmei

doi:10.3892/etm.2020.9284

Inhibition of miRNA‑29a regulates intestinal barrier function in diarrhea‑predominant irritable bowel syndrome by upregulating ZO‑1 and CLDN1

Authors:
- He Zhu
- Xi Xiao
- Yuying Shi
- Yingxiu Wu
- Yusheng Huang
- Detang Li
- Fen Xiong
- Guodong He
- Yuna Chai
- Hongmei Tang
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Affiliations: Pharmaceutical Department, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R China, First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Pharmaceutical, First Affiliated Hospital of Zhengzhou University of Chinese Medicine, Zhengzhou, Henan 450052, P.R. China
Published online on: October 6, 2020 https://doi.org/10.3892/etm.2020.9284
Article Number: 155
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diarrhea‑predominant irritable bowel syndrome (IBS‑D) is a common chronic functional gastrointestinal disorder. MicroRNAs (miRNAs) have been identified to be involved in different physiological and pathological processes. In this study, the role of miRNA‑29a in the potential mechanism underlying the function of the intestinal mucosal barrier in IBS‑D was analyzed. Human intestinal mucosal epithelia from patients with IBS‑D (diagnosed as meeting the Rome IV criteria) and healthy volunteers were collected. An IBS‑D mouse model was established via induction with trinitro‑benzene‑sulfonic acid (TNBS), and the mice were injected with miRNA‑29a inhibitor. Using transmission electron microscopy (TEM), the epithelial ultrastructure of the human intestinal mucosa was examined. Using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis, the expression level of miRNA‑29a was assessed. ELISA was used to analyze the activity of D‑lactate (D‑LA) and diamine oxidase (DAO). Through immunohistochemistry, RT‑qPCR and western blotting, the expression of tight junction protein ZO‑1 (ZO‑1) and claudin‑1 (CLDN1) was examined. In the human intestinal mucosal epithelia from patients with IBS‑D, miRNA‑29a was upregulated, ZO‑1 and CLDN1 were downregulated, and the junctional complex (JC) was faint and discontinuous. In the IBS‑D mouse model, treatment with miRNA‑29a inhibitor downregulated D‑LA and DAO activity, and increased the expression of ZO‑1 and CLDN1 in the intestinal mucosal epithelium. In conclusion, the present study revealed that miRNA‑29a is involved in the pathogenesis of IBS‑D, probably by downregulating ZO‑1 and CLDN1 expression, suggesting that miRNA‑29a is likely to be an important regulator of intestinal barrier function and could be a possible therapeutic target for IBS‑D.

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