Alpízar-Alpízar Warner, Skindersoe Mette E, Rasmussen Lone, Kriegbaum Mette C, Christensen Ib J, Lund Ida K, Illemann Martin, Laerum Ole D, Krogfelt Karen A, Andersen Leif P, Ploug Michael
The Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, Denmark.
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2100 Copenhagen, Denmark.
Microorganisms. 2020 Jul 9;8(7):1019. doi: 10.3390/microorganisms8071019.
(1) Background: Persistent infection is the most important risk factor for gastric cancer. The urokinase receptor (uPAR) is upregulated in lesions harboring cancer invasion and inflammation. Circumstantial evidence tends to correlate colonization with increased uPAR expression in the human gastric epithelium, but a direct causative link has not yet been established in vivo; (2) Methods: In a mouse model of -induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to (SS1 strain) infection; (3) Results: We observed intense uPAR immunoreactivity in foveolar epithelial cells of the gastric corpus due to de novo synthesis, compared to non-infected animals. This uPAR induction represents a very early response, but it increases progressively over time as do infiltrating immune cells. Eradication of infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E treatment attenuates uPAR expression. Notwithstanding this relationship, does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.
(1) 背景：持续感染是胃癌最重要的危险因素。尿激酶受体（uPAR）在存在癌症侵袭和炎症的病变中上调。有间接证据表明，在人类胃上皮中，幽门螺杆菌定植与uPAR表达增加相关，但尚未在体内建立直接的因果联系；(2) 方法：在幽门螺杆菌诱导的胃炎小鼠模型中，我们研究了胃黏膜中uPAR蛋白表达随幽门螺杆菌（SS1菌株）感染的时间变化情况；(3) 结果：与未感染动物相比，我们观察到胃体部小凹上皮细胞中由于从头合成而出现强烈的uPAR免疫反应性。这种uPAR诱导是一种非常早期的反应，但随着时间的推移会逐渐增加，浸润的免疫细胞也是如此。通过抗菌治疗根除幽门螺杆菌感染会使uPAR表达恢复到其生理基线水平。用前列腺素E治疗抑制炎症反应会减弱uPAR表达。尽管存在这种关系，但幽门螺杆菌在与胃癌细胞系共培养时确实能在体外诱导uPAR表达；(4) 结论：我们表明，持续的幽门螺杆菌定植是小鼠胃上皮细胞中出现相对较高uPAR蛋白表达的必要条件。
