Furthermore, literature has shown that ischemia can activate PAR1 receptors, activating PKC-Akt and PKC-ERK1/2 pathways, and thereby increasing the release of matrix metalloproteinase-9 (MMP-9); MMP-9 degrades tight junction proteins such as occludin and claudin-5 (91). This evidence concerns the gene CLDN5 and ischemia.