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Cells
Volume 15
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10.3390/cells15020167
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention

by
Gracjana Krzysiek-Maczka
1,*,
Aneta Targosz
1,
Patrycja Bronowicka-Adamska
2,
Urszula Szczyrk
1,
Malgorzata Strzalka
1,
Hubert Mączka
3,
Mateusz Wierdak
4,
Izabela Rodzon
1,
Jaroslaw Czyz
5,
Tomasz Brzozowski
1,* and
Agata Ptak-Belowska
1
1
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland
2
Department of in Medical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, Mikolaja Kopernika 7c, 31-034 Cracow, Poland
3
Student Research Group, Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, Grzegorzecka 16, 31-531 Cracow, Poland
4
Department of Endoscopic, Metabolic and Soft Tissue Malignancies Surgery of University Hospital, Jagiellonian University, Jakubowskiego 2, 30-688 Cracow, Poland
5
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, Poland
*
Authors to whom correspondence should be addressed.
Cells 2026, 15(2), 167; https://doi.org/10.3390/cells15020167 (registering DOI)
Submission received: 3 November 2025 / Revised: 29 December 2025 / Accepted: 9 January 2026 / Published: 16 January 2026
(This article belongs to the Special Issue Molecular and Signaling Pathways in Pathological Changes of Esophageal, Gastric and Intestinal Epithelial Cells and Methods of Cell Protective Treatment)
Review Reports Versions Notes

Abstract

Early prevention of pathological changes underlying gastric cancer (GC) development is a critical strategy, offering the most effective opportunity to limit malignant progression and improve patient outcomes. We have previously demonstrated that Helicobacter pylori (Hp) (cagA+vacA+) contributes to GC development by activating gastric fibroblasts toward CAF-like phenotype, eliciting aggressive, cancer stem cells (CSCs)-related malignant transformation of LGR5+ normal epithelial cells. A key mediator of these processes appears to be the NF-κB/STAT3 axis. Therefore, our aim was to investigate the protective role of hydrogen sulfide (H2S) as a potential novel strategy for counteracting Hp-induced fibroblast reprogramming. Human fibroblasts were infected with Hp (cagA+vacA+) for 120 h. The fast-releasing H2S donor NaHS (50, 100, 200 and 400 µM) was added every 24 h. Activation markers, corresponding signaling pathways, H2S release and activities of H2S-metabolizing enzymes were determined. NaHS reduced Hp-induced fibroblast activation and their pro-inflammatory, pro-tumorigenic markers, which was associated with the inhibition of NF-κB/STAT3 axis and Twist expression. Additionally, it modulated sulfur metabolism while preserving sulfur-enzyme homeostasis. NaHS limited Hp adhesion (high doses), reduced reinfection-induced activation and increased sensitivity of Hp to metronidazole. These findings suggest that H2S signaling may represent a modulatory factor of NF-κB/STAT3-driven inflammatory responses during Hp infection and warrant further investigation.
Keywords: helicobacter pylori-activated fibroblasts; gastric cancer associated fibroblasts; NF-κB; STAT3; hydrogen sulfide (H2S) helicobacter pylori-activated fibroblasts; gastric cancer associated fibroblasts; NF-κB; STAT3; hydrogen sulfide (H2S)

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MDPI and ACS Style

Krzysiek-Maczka, G.; Targosz, A.; Bronowicka-Adamska, P.; Szczyrk, U.; Strzalka, M.; Mączka, H.; Wierdak, M.; Rodzon, I.; Czyz, J.; Brzozowski, T.; et al. Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention. Cells 2026, 15, 167. https://doi.org/10.3390/cells15020167

AMA Style

Krzysiek-Maczka G, Targosz A, Bronowicka-Adamska P, Szczyrk U, Strzalka M, Mączka H, Wierdak M, Rodzon I, Czyz J, Brzozowski T, et al. Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention. Cells. 2026; 15(2):167. https://doi.org/10.3390/cells15020167

Chicago/Turabian Style

Krzysiek-Maczka, Gracjana, Aneta Targosz, Patrycja Bronowicka-Adamska, Urszula Szczyrk, Malgorzata Strzalka, Hubert Mączka, Mateusz Wierdak, Izabela Rodzon, Jaroslaw Czyz, Tomasz Brzozowski, and et al. 2026. "Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention" Cells 15, no. 2: 167. https://doi.org/10.3390/cells15020167

APA Style

Krzysiek-Maczka, G., Targosz, A., Bronowicka-Adamska, P., Szczyrk, U., Strzalka, M., Mączka, H., Wierdak, M., Rodzon, I., Czyz, J., Brzozowski, T., & Ptak-Belowska, A. (2026). Hydrogen Sulfide Inhibits H. pylori-Induced Gastric Fibroblast Activation: Implications for Cancer Prevention. Cells, 15(2), 167. https://doi.org/10.3390/cells15020167

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