Figure 3.

TRPM2 in inflammation. (A) Leukocyte extravasation during inflammation. (B) TRPM2-mediated Ca²⁺ influx leads to tight-junction molecule degradation (VE-cadherin and occludin) and mitochondrial dysfunction in endothelial cells. (C) TRPM2-mediated Ca²⁺ influx is needed for immune cell migration and activation. During inflammation, ROS production in mitochondria is increased, which activates PARP in mitochondria or in the nucleus and enhances the production of ADPR. Increased ADPR potentiates TRPM2-mediated Ca²⁺ influx, which further increases the production of ROS in mitochondria, leading to the formation of a feed-forward vicious cycle. ROS-, PARP-, and Ca²⁺ -related signaling pathways increase the expression of proinflammatory genes, such as TNF-α, IL-1β, MCP1, and MIF. Moreover, TRPM2-mediated Ca²⁺ influx promotes cytoskeleton rearrangement and immune cell migration.