Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1741-1754
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1741
Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptide-expressing metaplasia lesions
Wan-Qun Chen, Feng-Liang Tian, Jin-Wei Zhang, Xiao-Jun Yang, Yan-Ping Li
Wan-Qun Chen, Feng-Liang Tian, Xiao-Jun Yang, Yan-Ping Li, Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400000, China
Jin-Wei Zhang, Department of Dermatology and Cosmetology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400000, China
Author contributions: Yang XJ and Li YP contributed equally to this work; Chen WQ, Tian FL, Yang XJ and Li YP designed the research study; Chen WQ and Zhang JW performed the research; Tian FL and Zhang JW contributed new reagents and analytic tools; Chen WQ, Yang XJ and Li YP analyzed the data and wrote the manuscript; All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81904175; Natural Science Foundation of Chongqing, China, No. cstc2018jcyjAX0756; and Chongqing Health Planning Commission Project, No. ZY201802063 and No. 2019ZY013111.
Institutional review board statement: The study was reviewed and approved by the Chongqing Hospital of Traditional Chinese Medicine Institutional Review Board (Approval No.2019-ky-25).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Chongqing Hospital of Traditional Chinese Medicine (IACUC protocol number: [Protocol No. 2020-DWKY-01]).
Conflict-of-interest statement: The authors declared that they have no conflicts of interest in this work.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Ping Li, PhD, Professor, Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, No. 6 Panxi Qizhi Road, Jiangbei District, Chongqing 400000, China. lyp20210203@163.com
Received: June 3, 2021
Peer-review started: June 3, 2021
First decision: June 30, 2021
Revised: July 10, 2021
Accepted: August 24, 2021
Article in press: August 24, 2021
Published online: November 15, 2021
Abstract
BACKGROUND

Spasmolytic polypeptide-expressing metaplasia (SPEM) is a potential preneoplastic lesion.

AIM

To elucidate the microRNA (miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules (YWXY) in SPEM lesions.

METHODS

Gastric mucosa biopsies were collected from chronic atrophic gastritis patients and healthy people with signed informed consent. YWXY was administered to the mice with induced SPEM by tamoxifen, and the gastric mucosa was harvested on the tenth day of the experiment. Then immunohistochemistry and immunofluorescence were performed to validate the SPEM, lesions and the potential mechanism was investigated. RNA transcripts were detected with reverse transcription-quantitative polymerase chain reaction.

RESULTS

The expression of miR-7 was downregulated in the SPEM lesions, and expression of trefoil factor 2 (TFF2) and clusterin was high in the human gastric mucosa. In vivo experiments showed that YWXY could inhibit the cell proliferation in the tamoxifen-induced SPEM lesions by regulating Ki67. Simultaneously, YWXY could restore the expression of miR-7 by regulating TFF2 by detection with immunofluorescence but not with reverse transcription-quantitative polymerase chain reaction, indicating its potential mechanism of targeting miR-7 by mediating TFF2. The expression of vascular endothelial growth factor-β and gastric intrinsic factor was restored within 3 d of YWXY administration for the SPEM lesions, speculating that the possible mechanism of YWXY is to inhibit the development and progression of SPEM by regulating vascular endothelial growth factor-β and gastric intrinsic factor.

CONCLUSION

miR-7 downregulation is an early event in SPEM through regulation of TFF2 in human gastric mucosa. YWXY is able to inhibit the cell proliferation and restore the expression of miR-7 by mediating TFF2 in the SPEM mouse model.

Keywords: Spasmolytic polypeptide-expressing metaplasia, Yiwei Xiaoyu Granules, MicroRNA-7, Chronic atrophic gastritis, Trefoil factor 2, Gastric precancerous lesions

Core Tip: We showed evidence that microRNA-7 downregulation is an early event in the cascade from metaplasia to gastric cancer and that it contributes to the establishment of an intestinal expression profile through regulation of trefoil factor 2 in both human gastric mucosa and in vivo experiments. To the best of our knowledge, we used the spasmolytic polypeptide-expressing metaplasia mouse model for the first time to reveal the effectiveness and the potential mechanism of Chinese medicine Yiwei Xiaoyu granules for the precursor of gastric adenocarcinoma.