Chen Wan-Qun, Tian Feng-Liang, Zhang Jin-Wei, Yang Xiao-Jun, Li Yan-Ping
Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400000, China.
Department of Dermatology and Cosmetology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400000, China.
World J Gastrointest Oncol. 2021 Nov 15;13(11):1741-1754. doi: 10.4251/wjgo.v13.i11.1741.
Spasmolytic polypeptide-expressing metaplasia (SPEM) is a potential preneoplastic lesion.
To elucidate the microRNA (miR)-7-mediated preventive and inhibitive effects of Yiwei Xiaoyu granules (YWXY) in SPEM lesions.
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.
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. 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.
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.
表达解痉多肽的化生(SPEM)是一种潜在的癌前病变。
阐明益胃消瘀颗粒(YWXY)对SPEM病变的微小RNA(miR)-7介导的预防和抑制作用。
收集签署知情同意书的慢性萎缩性胃炎患者和健康人的胃黏膜活检组织。用他莫昔芬诱导小鼠发生SPEM后给予YWXY,在实验第10天采集胃黏膜。然后进行免疫组织化学和免疫荧光以验证SPEM病变,并研究潜在机制。用逆转录-定量聚合酶链反应检测RNA转录本。
在SPEM病变中miR-7表达下调,三叶因子2(TFF2)和聚集素在人胃黏膜中表达较高。实验表明,YWXY可通过调节Ki67抑制他莫昔芬诱导的SPEM病变中的细胞增殖。同时,通过免疫荧光检测发现YWXY可通过调节TFF2恢复miR-7的表达,但逆转录-定量聚合酶链反应检测未发现此现象,表明其通过介导TFF2靶向miR-7的潜在机制。对于SPEM病变,给予YWXY 3天内血管内皮生长因子-β和胃内因子的表达得以恢复,推测YWXY的可能机制是通过调节血管内皮生长因子-β和胃内因子来抑制SPEM的发生和发展。
miR-7下调是人类胃黏膜中通过调节TFF2发生SPEM的早期事件。在SPEM小鼠模型中,YWXY能够通过介导TFF2抑制细胞增殖并恢复miR-7的表达。