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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 Oct 05;25(19)

Date

10/16/2024

Pubmed ID

39409043

Pubmed Central ID

PMC11605242

DOI

10.3390/ijms251910714

Scopus ID

2-s2.0-85206446606 (requires institutional sign-in at Scopus site)

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.

Author List

Ergun P, Samuels TL, Mathison AJ, Plehhova K, Coyle C, Horvath L, Johnston N

Authors

Pelin Ergun PhD Postdoctoral Researcher 1 in the Otolaryngology department at Medical College of Wisconsin
Nikki Johnston PhD Professor in the Otolaryngology department at Medical College of Wisconsin
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Topical
Alginates
Epithelial Cells
Gastroesophageal Reflux
Gene Expression Profiling
Humans
Pepsin A
Proton Pump Inhibitors
Transcriptome