Mechanistically, HGF inhibits inflammatory M1-like macrophage production of pro-inflammatory cytokines and chemokines (such as IL-1, IL-6, TNF, CXCL1, CXCL10, and CCL2) by disrupting nuclear factor NF-B signaling (Giannopoulou et al., 2008) through the enhancement of the heme oxygenase-1 (HO-1) transcriptional pathway and the inactivation of the GSK-3 pathway (Kamimoto et al., 2009a,b
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This selectivity stems from the unique dependence of senescent cells on the FOXO4-p53 interaction for survival, a vulnerability not present in proliferating or quiescent healthy cells
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