Pyroptosis in gastric mucosal injury‑related diseases (Review)

Abstract

Gastric mucosal epithelial cells, immune cells and signaling molecules constitute the innate and adaptive immune systems of the gastric mucosa, working together to maintain its integrity. Once the balance is disrupted, gastric mucosal diseases may occur. Pyroptosis, as a unique inflammatory programmed cell death mechanism, participates in the dynamic balance between innate and adaptive immunity by identifying and responding to damage factors, and participating in the maturation and release process of inflammatory factors. Pyroptosis is involved in the association of gastric mucosal resistance with microbial invasion and endogenous damage. By releasing inflammatory factors, the immune environment of the gastric mucosa is reshaped, thereby affecting repair mechanisms and the specific direction of cell differentiation. The present review summarizes the important role of pyroptosis in focal and diffuse gastric mucosal injury. The review aims to provide a novel theoretical basis for the optimization of prevention strategies and treatment plans for current gastric mucosal diseases, and proposes a new option for the scientific management of these diseases.

Keywords: diffuse gastric mucosal injury; focal gastric mucosal injury; gastric mucosal diseases; pyroptosis.

Figure 1

Role of pyroptosis in gastric mucosal injury-related diseases, including both focal injuries (such as stress-induced gastric mucosal injury and gastric ulcers) and diffuse injuries, which can be initiated by AIG, and include SPEM, GC and gastric MALT lymphoma. AIG, autoimmune gastritis; SPEM, spasmolytic polypeptide-expressing metaplasia; GC, gastric cancer; MALT lymphoma, mucosa-associated lymphoid tissue lymphoma.

Figure 2

Pyroptosis participates in the regulation of the immune microenvironment of autoimmune gastritis by affecting CD4⁺ T cells. GSDMB, gasdermin B; IFNγ, interferon γ; IFNγ, IFNγ receptor; NLRP3, nucleotide-binding domain and leucine-rich repeat protein 3; ROS, reactive oxygen species; Th, T helper; PCA, parietal cell antibody.

Figure 3

Parietal cells are regulated by mitochondrial GRIM-19 and activate the NLRP3 inflammasome through the ROS/NRF2/HO-1/NF-κB axis, initiating the classical pyroptosis pathway. GRIM-19, gene associated with retinoid-interferon-induced mortality 19; GSDMD, gasdermin D; HO-1, heme oxygenase-1; NLRP3, nucleotide-binding domain and leucine-rich repeat protein 3; NRF2, nuclear factor (erythroid-derived 2)-like 2; ROS, reactive oxygen species; SPEM, spasmolytic polypeptide-expressing metaplasia.