Preventive and inhibitive effects of Yiwei Xiaoyu granules on the development and progression of spasmolytic polypeptideexpressing metaplasia lesions

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 transcriptionquantitative 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-βand 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-βand 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.