Hmgb1, also known as High mobility group box-1 protein 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 plays a crucial role in innate immune responses. It is released from activated innate immune cells or necrotic cells and functions in pathways related to inflammation, such as in endotoxemia, sepsis, arthritis, and local inflammation [1].

In zebrafish, anti-sense Hmgb1 morpholinos (a form of loss-of-function experiment) inhibited locomotor recovery by 34% and decreased axonal regeneration by 34% after spinal cord injury, suggesting that Hmgb1 promotes recovery from spinal cord injury through enhancing neuroregeneration and angiogenesis [2]. Also, riboflavin, which can inhibit Hmgb1 release, showed time-dependent efficacy in reducing the expression and release of Hmgb1 during zymosan-induced inflammation, indicating its potential as a therapeutic agent related to Hmgb1-mediated inflammation [3].

In conclusion, Hmgb1 has dual functions in the nucleus and extracellular space. In the nucleus, it is involved in DNA-related processes, while extracellularly, it acts as a pro-inflammatory mediator. Studies in zebrafish and with riboflavin's effect on Hmgb1 release have provided insights into its role in inflammation-related diseases and tissue regeneration. Understanding Hmgb1 is crucial for developing potential therapeutic strategies for various inflammatory diseases and spinal cord injury recovery.