Chirico Valeria, Lacquaniti Antonio, Salpietro Vincenzo, Munafò Caterina, Calabrò Maria Pia, Buemi Michele, Arrigo Teresa, Salpietro Carmelo
Department of Pediatric Sciences, University of Messina, 98100, Messina, Italy,
Eur J Pediatr. 2014 Sep;173(9):1123-36. doi: 10.1007/s00431-014-2327-1. Epub 2014 May 9.
High-mobility group box protein 1 (HMGB1) is a nonhistone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 activates the innate system and mediates a wide range of physiological and pathological responses. HMGB1 exerts these actions through differential engagement of multiple surface receptors, including Toll-like receptor (TLR)2, TLR4, and receptor for advanced glycation end products (RAGE). HMGB1 is implicated as a late mediator of sepsis and is also involved in inflammatory and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Interestingly, HMGB1 was associated with tumor progression, becoming a potential therapeutic target, due to its involvement in the resistance to chemotherapy. Its implication on the pathogenesis of systemic vasculitis and inflammatory bowel diseases has also been evaluated. Moreover, it regulates neuroinflammation after traumatic brain injuries or cerebral infectious diseases. The aim of this review is to analyze these different roles of HMGB1, both in physiological and pathological conditions, discussing clinical and scientific implications in the field of pediatrics.
HMGB1 plays a key role in several pediatric diseases, opening new scenarios for diagnostic biomarkers and therapeutic strategies development.
高迁移率族蛋白B1（HMGB1）是一种具有双重功能的非组蛋白核蛋白。在细胞内，HMGB1与DNA结合，调节转录并决定染色体结构。在细胞外，HMGB1激活先天性免疫系统并介导多种生理和病理反应。HMGB1通过与多种表面受体（包括Toll样受体（TLR）2、TLR4和晚期糖基化终产物受体（RAGE））的不同结合来发挥这些作用。HMGB1被认为是脓毒症的晚期介质，还参与炎症和自身免疫性疾病，如类风湿性关节炎和系统性红斑狼疮。有趣的是，由于HMGB1参与化疗耐药，它与肿瘤进展相关，成为一个潜在的治疗靶点。其在系统性血管炎和炎症性肠病发病机制中的作用也已得到评估。此外，它在创伤性脑损伤或脑部感染性疾病后调节神经炎症。本综述的目的是分析HMGB1在生理和病理条件下的这些不同作用，讨论儿科学领域的临床和科学意义。
HMGB1在几种儿科疾病中起关键作用，为诊断生物标志物和治疗策略的开发开辟了新的前景。
