Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.

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.