Extracellular HMGB1, a Signal of Tissue Damage, Induces Mesoangioblast Migration and Proliferation

• Published in: The Journal of cell biology Vol. 164; no. 3; pp. 441 - 449
• Main Authors: Palumbo, Roberta, Sampaolesi, Maurilio, De Marchis, Francesco, Tonlorenzi, Rossana, Colombetti, Sara, Mondino, Anna, Cossu, Giulio, Bianchi, Marco E.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.02.2004; The Rockefeller University Press
• Subjects: Anger; Animals; Bone marrow cells; Cattle; Cell adhesion & migration; Cell Division - physiology; Cell growth; Cell Movement - physiology; Cell Transplantation; Cells; Cells, Cultured; Cellular biology; Cytokines; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Embryo, Mammalian - physiology; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; HMGB1 Protein - metabolism; Homing; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred Strains; Mice, Knockout; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; Muscles; Receptor for Advanced Glycation End Products; Receptors; Receptors, Immunologic - metabolism; Regeneration - physiology; Sarcoglycans; Stem cells; Stem Cells - cytology; Stem Cells - physiology; Tissues
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200304135

High mobility group box 1 (HMGB1) is an abundant chromatin protein that acts as a cytokine when released in the extracellular milieu by necrotic and inflammatory cells. Here, we show that extracellular HMGB1 and its receptor for advanced glycation end products (RAGE) induce both migration and proliferation of vessel-associated stem cells (mesoangioblasts), and thus may play a role in muscle tissue regeneration. In vitro, HMGB1 induces migration and proliferation of both adult and embryonic mesoangioblasts, and disrupts the barrier function of endothelial monolayers. In living mice, mesoangioblasts injected into the femoral artery migrate close to HMGB1-loaded heparin-Sepharose beads implanted in healthy muscle, but are unresponsive to control beads. Interestingly, α-sarcoglycan null dystrophic muscle contains elevated levels of HMGB1; however, mesoangioblasts migrate into dystrophic muscle even if their RAGE receptor is disabled. This implies that the HMGB1-RAGE interaction is sufficient, but not necessary, for mesoangioblast homing; a different pathway might coexist. Although the role of endogenous HMGB1 in the reconstruction of dystrophic muscle remains to be clarified, injected HMGB1 may be used to promote tissue regeneration.