We next investigated the role of TRPM2 activation in EC barrier function and ZO-1 degradation. TRPM2 neutralizing antibody (5 μg/ml, 4 hr pretreatment) significantly prevented ZO-1 degradation induced by PM ( Figure 4A ). TRPM2 siRNA (100 ng/ml), which downregulated TRPM2 protein level ( Figure 4B ), also inhibited PM-induced ZO-1 degradation ( Figure 4C ). In parallel, antagonizing TRPM2 by either TRPM2 antibody (5 μg/ml, 4 hr pretreatment) or TRPM2 siRNA (100 ng/ml) significantly prevented PM-induced EC barrier disruption ( Figure 4D-E) , as indicated by TER measurements.