PDF(Pubmed)
Abstract：
Helicobacter pylori (H. pylori) infection is the primary risk factor for the progress of gastric diseases. The persistent stomach colonization of H. pylori is closely associated with the development of gastritis and malignancies. Although the involvement of progranulin (PGRN) in various cancer types has been well-documented, its functional role and underlying mechanisms in gastric cancer (GC) associated with H. pylori infection remain largely unknown. This report demonstrated that PGRN was up-regulated in GC and associated with poor prognosis, as determined through local and public database analysis. Additionally, H. pylori induced the up-regulation of PGRN in gastric epithelial cells both in vitro and in vivo. Functional studies have shown that PGRN promoted the intracellular colonization of H. pylori. Mechanistically, H. pylori infection induced autophagy, while PGRN inhibited autophagy to promote the intracellular colonization of H. pylori. Furthermore, PGRN suppressed H. pylori-induced autophagy by down-regulating decorin (DCN) through the mTOR pathway. In general, PGRN inhibited autophagy to facilitate intracellular colonization of H. pylori via the PGRN/mTOR/DCN axis. This study provides new insights into the molecular mechanisms underlying the progression of gastric diseases, suggesting PGRN as a potential therapeutic target and prognostic predictor for these disorders.
摘要：
幽门螺杆菌(H.pylori)感染是胃病进展的主要危险因素。幽门螺杆菌持续的胃部定植与胃炎和恶性肿瘤的发生发展密切相关。尽管颗粒蛋白前体（PGRN）在各种癌症类型中的参与已经得到了充分的证明，其在与幽门螺杆菌感染相关的胃癌(GC)中的功能作用和潜在机制尚不清楚.该报告表明PGRN在GC中上调，并与不良预后相关。通过本地和公共数据库分析确定。此外,幽门螺杆菌在体外和体内均诱导胃上皮细胞中PGRN的上调。功能研究表明PGRN促进幽门螺杆菌的细胞内定植。机械上,幽门螺杆菌感染诱导自噬，而PGRN抑制细胞自噬促进H.pylori细胞内定植。此外，PGRN通过mTOR通路下调核心蛋白聚糖(DCN)抑制幽门螺杆菌诱导的自噬。总的来说,PGRN通过PGRN/mTOR/DCN轴抑制自噬以促进幽门螺杆菌的细胞内定植。这项研究为胃疾病进展的分子机制提供了新的见解，提示PGRN是这些疾病的潜在治疗靶点和预后预测因子。
