Published online October 8, 2007
doi:10.1083/jcb.200704015
The Journal of Cell Biology, Vol. 179, No. 1, 33-40
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Palumbo et al.
Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-
B activation
Roberta Palumbo1,
Beatriz G. Galvez2,
Tobias Pusterla1,
Francesco De Marchis1,
Giulio Cossu2,3,
Kenneth B. Marcu4,5, and
Marco E. Bianchi1,6
1 Chromatin Dynamics Unit and 2 Stem Cell Research Institute, Istituto Scientifico San Raffaele, 20132 Milan, Italy
3 Department of Biology and Centre for Stem Cell Research, University of Milan, 20133 Milan, Italy
4 Centro di Ricerca Biomedica Applicata, Policlinico S. Orsola-Malpighi, Università di Bologna, 40138 Bologna, Italy
5 Biochemistry and Cell Biology Department, Institute for Cell and Developmental Biology, Stony Brook University, Stony Brook, NY 11794
6 Faculty of Medicine, San Raffaele University, 20132 Milan, Italy
Correspondence to Marco E. Bianchi: bianchi.marco{at}hsr.it
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
B (NF-
B) pathway via extracellular signal-regulated kinase phosphorylation. NF-
B 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-
B–activating signal tumor necrosis factor
. In dystrophic mice, mesoangioblasts injected into the general circulation ingress inefficiently into muscles if their NF-
B signaling pathway is disabled. These findings suggest that NF-
B signaling controls tissue regeneration in addition to early events in inflammation.
K.B. Marcu and M.E. Bianchi contributed equally to this paper.
Abbreviations used in this paper:
-SG,
-sarcoglycan; DRB, 5,6-dichloro-1-ß-D- ribobenzimidazole; ERK, extracellular signal-regulated kinase; fMLP, formyl-met-leu-phe; HMGB1, high mobility group box 1; IKK, I
B kinase; I
B
SR, I
B
super-repressor; MEF, mouse embryonic fibroblast; MEK, MAPK/ERK kinase; NF-
B, nuclear factor
B; RAGE, receptor for advanced glycation end products; SDF, stromal derived factor; wt, wild type.

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