<i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis
(1) Background: Persistent <i>Helicobacter pylori</i> 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 <i>H. pylori</i>...
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| Format: | Article |
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MDPI AG
2020-07-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/7/1019 |
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| author | Warner Alpízar-Alpízar Mette E. Skindersoe Lone Rasmussen Mette C. Kriegbaum Ib J. Christensen Ida K. Lund Martin Illemann Ole D. Laerum Karen A. Krogfelt Leif P. Andersen Michael Ploug |
| author_facet | Warner Alpízar-Alpízar Mette E. Skindersoe Lone Rasmussen Mette C. Kriegbaum Ib J. Christensen Ida K. Lund Martin Illemann Ole D. Laerum Karen A. Krogfelt Leif P. Andersen Michael Ploug |
| author_sort | Warner Alpízar-Alpízar |
| collection | DOAJ |
| description | (1) Background: Persistent <i>Helicobacter pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i>-induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to <i>H. pylori</i> (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 <i>H. pylori</i> infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E<sub>2</sub> treatment attenuates uPAR expression. Notwithstanding this relationship, <i>H. pylori</i> does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent <i>H. pylori</i> colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells. |
| first_indexed | 2024-03-10T18:34:37Z |
| format | Article |
| id | doaj.art-7900885cc62f42c894a2eb8f073e1fdf |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T18:34:37Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-7900885cc62f42c894a2eb8f073e1fdf2023-11-20T06:21:16ZengMDPI AGMicroorganisms2076-26072020-07-0187101910.3390/microorganisms8071019<i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early PathogenesisWarner Alpízar-Alpízar0Mette E. Skindersoe1Lone Rasmussen2Mette C. Kriegbaum3Ib J. Christensen4Ida K. Lund5Martin Illemann6Ole D. Laerum7Karen A. Krogfelt8Leif P. Andersen9Michael Ploug10The Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Bacteria, Parasites and Fungi, Statens Serum Institute, 2300 Copenhagen, DenmarkDepartment of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Bacteria, Parasites and Fungi, Statens Serum Institute, 2300 Copenhagen, DenmarkDepartment of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, DenmarkThe Finsen Laboratory, Rigshospitalet, 2100 Copenhagen, Denmark(1) Background: Persistent <i>Helicobacter pylori</i> 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 <i>H. pylori</i> 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 <i>H. pylori</i>-induced gastritis, we investigated the temporal emergence of uPAR protein expression in the gastric mucosa in response to <i>H. pylori</i> (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 <i>H. pylori</i> infection by antimicrobial therapy causes a regression of uPAR expression to its physiological baseline levels. Suppression of the inflammatory response by prostaglandin E<sub>2</sub> treatment attenuates uPAR expression. Notwithstanding this relationship, <i>H. pylori</i> does induce uPAR expression in vitro in co-cultures with gastric cancer cell lines; (4) Conclusions: We showed that persistent <i>H. pylori</i> colonization is a necessary event for the emergence of a relatively high uPAR protein expression in murine gastric epithelial cells.https://www.mdpi.com/2076-2607/8/7/1019uPAR<i>Helicobacter pylori</i>gastric cancergastritismucous metaplasiamouse model |
| spellingShingle | Warner Alpízar-Alpízar Mette E. Skindersoe Lone Rasmussen Mette C. Kriegbaum Ib J. Christensen Ida K. Lund Martin Illemann Ole D. Laerum Karen A. Krogfelt Leif P. Andersen Michael Ploug <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis Microorganisms uPAR <i>Helicobacter pylori</i> gastric cancer gastritis mucous metaplasia mouse model |
| title | <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis |
| title_full | <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis |
| title_fullStr | <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis |
| title_full_unstemmed | <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis |
| title_short | <i>Helicobacter pylori</i> Colonization Drives Urokinase Receptor (uPAR) Expression in Murine Gastric Epithelium During Early Pathogenesis |
| title_sort | i helicobacter pylori i colonization drives urokinase receptor upar expression in murine gastric epithelium during early pathogenesis |
| topic | uPAR <i>Helicobacter pylori</i> gastric cancer gastritis mucous metaplasia mouse model |
| url | https://www.mdpi.com/2076-2607/8/7/1019 |
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