Leukocyte HMGB1 is required for vessel remodeling in regenerating muscles

Lara Campana, Francesco Santarella, Antonio Esposito, Norma Maugeri, Elena Rigamonti, Antonella Monno, Tamara Canu, Alessandro Del Maschio, Marco E. Bianchi, Angelo A. Manfredi, Patrizia Rovere-Querini

Research output: Contribution to journalArticlepeer-review


Signals of tissue necrosis, damage-associated molecular patterns (DAMPs), cause inflammation. Leukocytes migrating into injured tissues tonically release DAMPs, including the high mobility group box 1 protein (HMGB1). In the absence of suitable models, the relative role of DAMPs released because of necrosis or leukocyte activation has not, so far, been dissected. We have generated a mouse model lacking Hmgb1 in the hematopoietic system and studied the response to acute sterile injury of the skeletal muscle. Regenerating fibers are significantly less numerous at earlier time points and smaller at the end of the process. Leukocyte Hmgb1 licenses the skeletal muscle to react to hypoxia, to express angiopoietin-2, and to initiate angiogenesis in response to injury. Vascularization of the regenerating tissue is selectively jeopardized in the absence of leukocyte Hmgb1, revealing that it controls the nutrient and oxygen supply to the regenerating tissue. Altogether, our results reveal a novel nonredundant role for leukocyte Hmgb1 in the repair of injured skeletal muscle.

Original languageEnglish
Pages (from-to)5257-5264
Number of pages8
JournalJournal of Immunology
Issue number11
Publication statusPublished - Jun 1 2014

ASJC Scopus subject areas

  • Immunology


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