Recent advances in spasmolytic polypeptide expressing metaplasia research

Figure 3 Interaction of key factors upstream and downstream of spasmolytic polypeptide-expressing metaplasia-related signaling pathway. The figure illustrates the molecular regulatory mechanisms associated with parietal cells and the spasmolytic polypeptide-expressing metaplasia signaling pathway, as evidenced in mouse models. In parietal cells, NLR family pyrin domain-containing 3 is activated by factors such as PR55, promoting the production of cytokines including interleukin (IL)-1β, IL-33, IL-8, and tumor necrosis factor-α. Concurrently, reactive oxygen species contribute to this regulation by activating nuclear factor erythroid 2-related factor 2, which subsequently modulates downstream effectors such as heme oxygenase-1. Within the spasmolytic polypeptide-expressing metaplasia signaling pathway, alterations in gene associated with retinoid-interferon-induced mortality 19 influence reactive oxygen species levels, thereby engaging in subsequent pathways, such as those involving bone morphogenetic protein. Additionally, key molecules including Yes-associated protein, telomerase reverse transcriptase, and β-catenin participate in the regulation of gene expression. For instance, lipocalin 2 expression is regulated by phosphorylated signal transducer and activator of transcription 3 within relevant signaling cascades, whereas the binding of sulforaphane to epidermal growth factor receptor activates a series of signal transduction events, such as the extracellular signal-regulated kinase pathway. Collectively, these interactions form a complex molecular regulatory network, as characterized by mouse studies. NLRP3: NLR family pyrin domain-containing 3; HO-1: Heme oxygenase-1; SPEM: Spasmolytic polypeptide-expressing metaplasia; NRF2: Nuclear factor erythroid 2-related factor 2; ROS: Reactive oxygen species; GRIM-19: Gene associated with retinoid-interferon-induced mortality 19; BMP: Bone morphogenetic protein; IL: Interleukin; TNF: Tumor necrosis factor; Sfn: Sulforaphane; TAM: Tamoxifen; CagA: Cytotoxin-associated gene A; EGFR: Epidermal growth factor receptor; YAP: Yes-associated protein; SYVN1: E3 ubiquitin ligase synoviolin; ERK: Extracellular signal-regulated kinase; stat3: Signal transducer and activator of transcription 3; Ddit4: DNA damage induced transcript 4; TERT: Telomerase reverse transcriptase; Sox9: SRY-Box transcription factor 9; LCN2: Lipocalin-2.