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Mol Aspects Med. 2014 Dec;40:1-116. doi: 10.1016/j.mam.2014.05.001. Epub 2014 Jul 8.

HMGB1 in health and disease.

Author information

1
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. Electronic address: kangr@upmc.edu.
2
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
3
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
4
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
5
Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
6
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
7
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Experimental Department of Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
8
Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
9
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. Electronic address: tangd2@upmc.edu.

Abstract

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed high-mobility group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhibitors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localization, structure, post-translational modification, and identification of additional partners will undoubtedly uncover additional secrets regarding HMGB1's multiple functions.

KEYWORDS:

Biology; DAMP; Disease; HMGB1

PMID:
25010388
PMCID:
PMC4254084
DOI:
10.1016/j.mam.2014.05.001
[Indexed for MEDLINE]
Free PMC Article
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