Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis
Background and Aims: While most Helicobacter pylori-infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium c...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Gastro Hep Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772572323000420 |
| _version_ | 1797777414581911552 |
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| author | Sohinee Sarkar Ghazal Alipour Talesh Trevelyan R. Menheniott Philip Sutton |
| author_facet | Sohinee Sarkar Ghazal Alipour Talesh Trevelyan R. Menheniott Philip Sutton |
| author_sort | Sohinee Sarkar |
| collection | DOAJ |
| description | Background and Aims: While most Helicobacter pylori-infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium channel regulatory subunit, SUR2 (encoded by ABCC9), with potential to protect against H pylori-associated diseases. Methods: SUR2 gene (ABCC9) expression in human gastric biopsies was analyzed by quantitative polymerase chain reactions. Helicobacter-infected mice were administered the SUR2-channel agonists, pinacidil and nicorandil, then gastric tissues analyzed by histology, immunohistochemistry and quantitative polymerase chain reaction, and splenic tissues by enzyme-linked immunosorbent assays. In vitro studies were performed on human and mouse macrophages, human gastric epithelial cells and mouse splenocytes. Results: ABCC9 expression in human and mouse stomachs is downregulated with H pylori infection. Treatment of Helicobacter-infected mice with SUR2 channel modulators, pinacidil or nicorandil, significantly reduced gastritis severity. In gastric epithelial cells, nicorandil-induced opening of the SUR2 channel increased intracellular K+ and prevented H pylori-mediated Ca2+ influx and downstream pro-inflammatory signaling. Conclusion: SUR2 is a novel host factor that regulates Helicobacter pathogenesis. Pharmacological targeting of SUR2 provides a potential approach for reducing the severity of H pylori-associated gastritis, without eradicating infection. |
| first_indexed | 2024-03-12T23:04:38Z |
| format | Article |
| id | doaj.art-6340bfeae76e46df990a202bcfc710d9 |
| institution | Directory Open Access Journal |
| issn | 2772-5723 |
| language | English |
| last_indexed | 2024-03-12T23:04:38Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Gastro Hep Advances |
| spelling | doaj.art-6340bfeae76e46df990a202bcfc710d92023-07-19T04:24:08ZengElsevierGastro Hep Advances2772-57232023-01-0125721732Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated GastritisSohinee Sarkar0Ghazal Alipour Talesh1Trevelyan R. Menheniott2Philip Sutton3Infection and Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Correspondence: Address correspondence to: Sohinee Sarkar, PhD, 50 Flemington Road, Parkville, Victoria 3030, Australia.Infection and Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaInfection and Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaInfection and Immunity, Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, AustraliaBackground and Aims: While most Helicobacter pylori-infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium channel regulatory subunit, SUR2 (encoded by ABCC9), with potential to protect against H pylori-associated diseases. Methods: SUR2 gene (ABCC9) expression in human gastric biopsies was analyzed by quantitative polymerase chain reactions. Helicobacter-infected mice were administered the SUR2-channel agonists, pinacidil and nicorandil, then gastric tissues analyzed by histology, immunohistochemistry and quantitative polymerase chain reaction, and splenic tissues by enzyme-linked immunosorbent assays. In vitro studies were performed on human and mouse macrophages, human gastric epithelial cells and mouse splenocytes. Results: ABCC9 expression in human and mouse stomachs is downregulated with H pylori infection. Treatment of Helicobacter-infected mice with SUR2 channel modulators, pinacidil or nicorandil, significantly reduced gastritis severity. In gastric epithelial cells, nicorandil-induced opening of the SUR2 channel increased intracellular K+ and prevented H pylori-mediated Ca2+ influx and downstream pro-inflammatory signaling. Conclusion: SUR2 is a novel host factor that regulates Helicobacter pathogenesis. Pharmacological targeting of SUR2 provides a potential approach for reducing the severity of H pylori-associated gastritis, without eradicating infection.http://www.sciencedirect.com/science/article/pii/S2772572323000420SUR2GastritisHelicobacter pyloriTherapeuticPotassium channel |
| spellingShingle | Sohinee Sarkar Ghazal Alipour Talesh Trevelyan R. Menheniott Philip Sutton Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis Gastro Hep Advances SUR2 Gastritis Helicobacter pylori Therapeutic Potassium channel |
| title | Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis |
| title_full | Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis |
| title_fullStr | Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis |
| title_full_unstemmed | Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis |
| title_short | Targeting Host Sulphonyl Urea Receptor 2 Can Reduce Severity of Helicobacter pylori Associated Gastritis |
| title_sort | targeting host sulphonyl urea receptor 2 can reduce severity of helicobacter pylori associated gastritis |
| topic | SUR2 Gastritis Helicobacter pylori Therapeutic Potassium channel |
| url | http://www.sciencedirect.com/science/article/pii/S2772572323000420 |
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