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Article

Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease

by
Pelin Ergun
1,
Tina L. Samuels
1,
Angela J. Mathison
2,
Kate Plehhova
3,
Cathal Coyle
3,
Lizzie Horvath
3 and
Nikki Johnston
1,*
1
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
2
Mellowes Center for Genomic Science and Precision Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
3
Reckitt Benckiser Healthcare UK Ltd., Slough SL1 3UH, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(19), 10714; https://doi.org/10.3390/ijms251910714
Submission received: 19 September 2024 / Revised: 1 October 2024 / Accepted: 3 October 2024 / Published: 5 October 2024

Abstract

Breakthrough symptoms are thought to occur in roughly half of all gastroesophageal reflux disease (GERD) patients despite maximal acid suppression (proton pump inhibitor, PPI) therapy. Topical alginates have recently been shown to enhance mucosal defense against acid-pepsin insult during GERD. We aimed to examine potential alginate protection of transcriptomic changes in a cell culture model of PPI-recalcitrant GERD. Immortalized normal-derived human esophageal epithelial cells underwent pretreatment with commercial alginate-based anti-reflux medications (Gaviscon Advance or Gaviscon Double Action), a matched-viscosity placebo control, or pH 7.4 buffer (sham) alone for 1 min, followed by exposure to pH 6.0 + pepsin or buffer alone for 3 min. RNA sequencing was conducted, and Ingenuity Pathway Analysis was performed with a false discovery rate of ≤0.01 and absolute fold-change of ≥1.3. Pepsin-acid exposure disrupted gene expressions associated with epithelial barrier function, chromatin structure, carcinogenesis, and inflammation. Alginate formulations demonstrated protection by mitigating these changes and promoting extracellular matrix repair, downregulating proto-oncogenes, and enhancing tumor suppressor expression. These data suggest molecular mechanisms by which alginates provide topical protection against injury during weakly acidic reflux and support a potential role for alginates in the prevention of GERD-related carcinogenesis.
Keywords: pepsin; gastroesophageal reflux disease; sodium alginate; Gaviscon; reflux; cancer; RNA sequencing; proton pump inhibitors pepsin; gastroesophageal reflux disease; sodium alginate; Gaviscon; reflux; cancer; RNA sequencing; proton pump inhibitors

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MDPI and ACS Style

Ergun, P.; Samuels, T.L.; Mathison, A.J.; Plehhova, K.; Coyle, C.; Horvath, L.; Johnston, N. Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease. Int. J. Mol. Sci. 2024, 25, 10714. https://doi.org/10.3390/ijms251910714

AMA Style

Ergun P, Samuels TL, Mathison AJ, Plehhova K, Coyle C, Horvath L, Johnston N. Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease. International Journal of Molecular Sciences. 2024; 25(19):10714. https://doi.org/10.3390/ijms251910714

Chicago/Turabian Style

Ergun, Pelin, Tina L. Samuels, Angela J. Mathison, Kate Plehhova, Cathal Coyle, Lizzie Horvath, and Nikki Johnston. 2024. "Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease" International Journal of Molecular Sciences 25, no. 19: 10714. https://doi.org/10.3390/ijms251910714

APA Style

Ergun, P., Samuels, T. L., Mathison, A. J., Plehhova, K., Coyle, C., Horvath, L., & Johnston, N. (2024). Global Transcriptomic Analysis of Topical Sodium Alginate Protection against Peptic Damage in an In Vitro Model of Treatment-Resistant Gastroesophageal Reflux Disease. International Journal of Molecular Sciences, 25(19), 10714. https://doi.org/10.3390/ijms251910714

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