IR stress increases MSC-mediated PGE2 section, which in turn activates macrophage Akt and phosphorylates β-catenin at Ser552 leading to translocation of β-catenin into nucleus. Notably, MSCs regulate macrophage Hippo-YAP pathway by depressing MST½ and LATS1 phosphorylation, and increasing YAP translocation from cytoplasm to nucleus where YAP co-localizes and interacts with nuclear β-catenin, which in turn regulates their target gene XBP1 leading to reduced NLRP3/caspase-1 activity and IL-1β release, and augmented M2 macrophage phenotype in IR-triggered liver inflammation.