Fig. 6: Schematic presentation of MMP9 mediated inhibition of reactive oxygen species (ROS) accumulation. | Cell Death & Disease

Fig. 6: Schematic presentation of MMP9 mediated inhibition of reactive oxygen species (ROS) accumulation.

From: Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer

Fig. 6: Schematic presentation of MMP9 mediated inhibition of reactive oxygen species (ROS) accumulation.The alternative text for this image may have been generated using AI.

In CAC, chronic inflammation generates ROS as well as activates MMP9. Active MMP9 is secreted out in extracellular space. MMP9 upregulates p53 expression via activation of transmembrane protein Notch111. Activation of p53 stimulates DNA damage response (DDR) to prevent ROS mediated DNA damage. DDR causes activation of mismatch repair (MMR) proteins to repair damaged DNA. This prevents the dysplasia progression and allows the proliferation of healthy epithelium. Preservation of healthy epithelium ensures the microbiota homeostasis and regulates ROS production. These events act as a positive feedback loop triggered by MMP9 causing the CAC suppression. Silencing of MMP9 accelerates CAC progression due to an auto feedback loop set up by the loss of microbiota and increase in ROS accumulation. This results in epithelial cell dysplasia in CAC.

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