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

作者：Roberta Palumbo, Beatriz G. Gálvez, Tobias Pusterla, Francesco De Marchis, Giulio Cossu, Kenneth B. Marcu, Marco E. Bianchi · 发表于：The Journal of Cell Biology · 年份：2007 · DOI：10.1083/jcb.200704015 · 被引用次数：247 · 研究领域：Advanced Glycation End Products research、Immune Response and Inflammation、NF-κB Signaling Pathways

Tissue damage is usually followed by healing, as both differentiated and stem cells migrate to replace dead or damaged cells. Mesoangioblasts (vessel-associated stem cells that can repair muscles) and fibroblasts migrate toward soluble factors released by damaged tissue. Two such factors are high mobility group box 1 (HMGB1), a nuclear protein that is released by cells undergoing unscheduled death (necrosis) but not by apoptotic cells, and stromal derived factor (SDF)-1/CXCL12. We find that HMGB1 activates the canonical nuclear factor kappaB (NF-kappaB) pathway via extracellular signal-regulated kinase phosphorylation. NF-kappaB signaling is necessary for chemotaxis toward HMGB1 and SDF-1/CXCL12, but not toward growth factor platelet-derived growth factor, formyl-met-leu-phe (a peptide that mimics bacterial invasion), or the archetypal NF-kappaB-activating signal tumor necrosis factor alpha. In dystrophic mice, mesoangioblasts injected into the general circulation ingress inefficiently into muscles if their NF-kappaB signaling pathway is disabled. These findings suggest that NF-kappaB signaling controls tissue regeneration in addition to early events in inflammation.