Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-κB activation

Tissue damage is usually followed by healing, as bothdifferentiated and stem cells migrate to replace deador damaged cells. Mesoangioblasts (vessel-associatedstem cells that can repair muscles) and fi broblasts migratetoward soluble factors released by damaged tissue. Twosuch factors are high mobility group box 1 (HMGB1), a nuclearprotein that is released by cells undergoing unscheduleddeath (necrosis) but not by apoptotic cells, and stromalderived factor (SDF)–1/CXCL12. We find that HMGB1activates the canonical nuclear factor κB (NF-κB) pathwayvia extracellular signal-regulated kinase phosphorylation.NF-κB signaling is necessary for chemotaxis towardHMGB1 and SDF-1/CXCL12, but not toward growth factorplatelet-derived growth factor, formyl-met-leu-phe(a peptide that mimics bacterial invasion), or the archetypalNF-κB–activating signal tumor necrosis factor α. In dystrophicmice, mesoangioblasts injected into the generalcirculation ingress inefficiently into muscles if their NF-κBsignaling pathway is disabled. These findings suggest thatNF-κB signaling controls tissue regeneration in additionto early events in inflammation