Hmgb1, also known as High mobility group box-1 protein (formerly HMG-1) or amphoterin, is a highly conserved and ubiquitous protein. Initially described as a nuclear DNA-binding protein involved in nucleosome stabilization and gene transcription, it also has extracellular functions. It is released from activated innate immune cells or necrotic cells, mediating processes like endotoxemia, sepsis, arthritis, and local inflammation, and thus is of great biological importance in immune-related pathways [1].

In adult zebrafish with spinal cord injury, application of anti-sense Hmgb1 morpholinos (a form of loss-of-function experiment) inhibited locomotor recovery by 34% and decreased axonal regeneration by 34% compared to control. This shows that Hmgb1 promotes recovery from spinal cord injury through enhancing neuroregeneration and angiogenesis [2]. In zymosan-induced inflammation in mice, riboflavin treatment significantly reduced both the expression and release of Hmgb1 in a time-dependent manner, suggesting its potential as a therapeutic target for inflammation-related conditions [3].

In conclusion, Hmgb1 has diverse functions. It plays a critical role in inflammation-related diseases such as sepsis, arthritis, and local inflammation. Studies in zebrafish and mice models have revealed its importance in processes like neuroregeneration and angiogenesis after spinal cord injury, as well as its regulation by riboflavin in inflammation. These findings highlight Hmgb1 as a potential therapeutic target in multiple disease areas.

References:

1. Chen, Guoqian, Ward, Mary F, Sama, Andrew E, Wang, Haichao. . Extracellular HMGB1 as a proinflammatory cytokine. In Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 24, 329-33. doi:. https://pubmed.ncbi.nlm.nih.gov/15212706/

2. Fang, Ping, Pan, Hong-Chao, Lin, Stanley Li, Schachner, Melitta, Shen, Yan-Qin. 2013. HMGB1 contributes to regeneration after spinal cord injury in adult zebrafish. In Molecular neurobiology, 49, 472-83. doi:10.1007/s12035-013-8533-4. https://pubmed.ncbi.nlm.nih.gov/23996344/

3. Mazur-Bialy, Agnieszka Irena, Pocheć, Ewa. 2015. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin. In Archivum immunologiae et therapiae experimentalis, 64, 171-6. doi:10.1007/s00005-015-0366-6. https://pubmed.ncbi.nlm.nih.gov/26445809/