Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine. Here we report that fully reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced glycation end products) are not involved. Injection of HMGB1 accelerates tissue repair by acting on resident muscle stem cells, hepatocytes, and infiltrating cells. The nonoxidizable HMGB1 mutant 3S, in which serines replace cysteines, promotes muscle and liver regeneration more efficiently than the wildtype protein and without exacerbating inflammation by selectively interacting with CXCR4. Overall, our results show that the reduced form of HMGB1 coordinates tissue regeneration and suggest that 3S may be used to safely accelerate healing after injury in diverse clinical contexts.

Tirone, M., Tran, N., Ceriotti, C., Gorzanelli, A., Canepari, M., Bottinelli, R., et al. (2018). High mobility group box 1 orchestrates tissue regeneration via CXCR4. JOURNAL OF EXPERIMENTAL MEDICINE, 215(1), 303-318 [10.1084/jem.20160217].

High mobility group box 1 orchestrates tissue regeneration via CXCR4

Tirone, Mario
Primo
;
Di Maggio, Stefania;François, Stéphanie;Conti, Valentina;CASALGRANDI, MAURA;Brunelli, Silvia
Penultimo
;
2018

Abstract

Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine. Here we report that fully reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced glycation end products) are not involved. Injection of HMGB1 accelerates tissue repair by acting on resident muscle stem cells, hepatocytes, and infiltrating cells. The nonoxidizable HMGB1 mutant 3S, in which serines replace cysteines, promotes muscle and liver regeneration more efficiently than the wildtype protein and without exacerbating inflammation by selectively interacting with CXCR4. Overall, our results show that the reduced form of HMGB1 coordinates tissue regeneration and suggest that 3S may be used to safely accelerate healing after injury in diverse clinical contexts.
Articolo in rivista - Articolo scientifico
HMGB1, tissue regeneration, satellite cells, macrophages, CXCR4, hepaocytes
English
2018
215
1
303
318
partially_open
Tirone, M., Tran, N., Ceriotti, C., Gorzanelli, A., Canepari, M., Bottinelli, R., et al. (2018). High mobility group box 1 orchestrates tissue regeneration via CXCR4. JOURNAL OF EXPERIMENTAL MEDICINE, 215(1), 303-318 [10.1084/jem.20160217].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/176767
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