Research progress in the inflammation-oxidative stress signaling network and stratified therapeutic interventions for gastroesophageal reflux disease

Abstract:

Gastroesophageal reflux disease (GERD) is a common chronic digestive disorder whose pathogenesis involves not only reflux-induced mucosal injury caused by gastric acid and bile acids but also persistent activation of inflammatory and oxidative stress responses. Emerging evidence indicates that reflux stimulation disrupts the esophageal epithelial barrier and promotes excessive generation of reactive oxygen species (ROS), leading to the activation of multiple signaling pathways, including TLR4/MyD88, NF-κB, MAPK, Nrf2, and IL-6/JAK/STAT3. These pathways interact to form an inflammation-oxidative stress network that drives disease progression and Barrett's esophagus development. This review summarizes recent advances in inflammation- and oxidative stress-related signaling pathways in GERD and proposes a stage-specific regulatory model consisting of inflammation initiation, signal amplification, oxidative stress imbalance, and chronic remodeling. Key molecular events and their interactions during disease progression are discussed. In addition, current and emerging therapeutic strategies, including proton pump inhibitors, potassium-competitive acid blockers, mucosal protective agents, and pathway-targeted interventions, are reviewed with respect to their mechanisms of action and research status. This stage-specific regulatory framework may provide new insights into the pathogenesis of GERD and offer a theoretical basis for mechanism-based precision therapy and future drug development.