The performance of the alarmin HMGB1 in pediatric diseases: From lab to clinic

Introduction: High-mobility group box protein 1 (HMGB1) is a ubiquitously expressed nonhistone nuclear protein that has multiple functions related to posttranslational modifications and cellular localization. In the nucleus, HMGB1 binds to DNA, regulating transcription and determining chromosomal architecture. When released into the extracellular space, HMGB1 activates innate immunity and mediates a wide range of physiological and pathological responses through the differential engagement of multiple surface receptors (i.e., TLR4/2 and RAGE). The effect of HMGB1-mediated inflammatory activation on different systems has received increasing attention. HMGB1 is implicated as a late mediator of sepsis and is also involved in inflammatory and autoimmune diseases. In addition, HMGB1 also affects the occurrence and progression of tumors. However, most studies involving HMGB1 have been focused on adults or mature animals. Due to differences in disease characteristics between children and adults, it is necessary to clarify the role of HMGB1 in pediatric diseases. Methods and Results: Through systematic database retrieval, this review aimed to first elaborate the characteristics of HMGB1 under physiological and pathological conditions and then discuss the clinical and scientific significance of HMGB1 in the pediatric field according to different systems. Conclusions: HMGB1 plays an important role in a variety of pediatric diseases and may be used as a diagnostic biomarker and therapeutic target for new strategies for the prevention and treatment of pediatric diseases.