Intestinal Mitogen-Activated Protein Kinase pathways and Nuclear Factor-kappa B signaling (MAPK/NF-κB signaling)

The intestinal Mitogen-Activated Protein Kinase (MAPK) pathways and Nuclear Factor-kappa B (NF-κB) signaling are fundamental regulatory networks that coordinate the gut's response to environmental stimuli and maintain mucosal homeostasis (PMID: 30103516). The MAPK cascade, including ERK, JNK, and p38, integrates signals from growth factors and stress to regulate intestinal epithelial cell proliferation, differentiation, and survival (PMID: 28545141). NF-κB acts as a central transcription factor that triggers the expression of pro-inflammatory cytokines and chemokines in response to microbial products or tissue damage (PMID: 21907251). Chronic dysregulation of these pathways is a hallmark of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, where persistent activation leads to tissue destruction and increases the risk of colorectal cancer (PMID: 25113315). Therapeutic interventions often target these pathways to dampen the inflammatory response, using agents like 5-aminosalicylates or corticosteroids, though the broad physiological importance of these signaling hubs necessitates careful management of potential side effects like immunosuppression (PMID: 11159025).

Other names

MAPK/NF-κB axisIntestinal inflammatory signaling pathwaysMAPK-NF-κB crosstalk

Drugs targeting these pathways typically act by inhibiting the phosphorylation of MAPK proteins (such as p38, JNK, or ERK) or by preventing the activation and nuclear translocation of the NF-κB transcription factor complex, thereby reducing the expression of pro-inflammatory genes (PMID: 11159025, 15181016).