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Abstract
When tissues are damaged, they usually heal. The cellular responses towards healing require the prior recognition that damage has occurred. High Mobility Group Box 1 protein (HMGB1) is a ubiquitous nuclear protein that is passively released by cells that have died in a traumatic, non-programmed way (necrosis). Several receptors for HMGB1 exist, and upon binding HMGB1 they alert leukocytes to extravasate from the blood into the affected tissue, trigger adaptive immunity and promote the migration and proliferation of cells (including stem cells) to repair the damaged tissue. Significantly, apoptotic cells modify their chromatin so as to bind HMGB1, which is not released. Several cell types (in particular inflammatory cells) when distressed have the ability to secrete HMGB1 actively, via a dedicated pathway, and thus produce a damage signal without dying. Because of its powerful activities, HMGB1 is involved in several disorders, including autoimmune ones.
Acknowledgements
We thank Ingrid E. Dumitriu for . Our lab is supported by the Italian Association for Cancer Research, the Association for International Cancer Research, the Ministry of University and Research, Fondazione Cariplo and Fondazione Monte dei Paschi di Siena. The authors declare no direct financial interest in this study. However, MEB is part-owner of HMGBiotech, a biotech company that sells HMGB1-related goods and services.