Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
Cell Biol Toxicol. 2024 Jul 15;40(1):55. doi: 10.1007/s10565-024-09893-2.
Drug-induced organic damage encompasses various intricate mechanisms, wherein HMGB1, a non-histone chromosome-binding protein, assumes a significant role as a pivotal hub gene. The regulatory functions of HMGB1 within the nucleus and extracellular milieu are interlinked. HMGB1 exerts a crucial regulatory influence on key biological processes including cell survival, inflammatory regulation, and immune response. HMGB1 can be released extracellularly from the cell during these processes, where it functions as a pro-inflammation cytokine. HMGB1 interacts with multiple cell membrane receptors, primarily Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE), to stimulate immune cells and trigger inflammatory response. The excessive or uncontrolled HMGB1 release leads to heightened inflammatory responses and cellular demise, instigating inflammatory damage or exacerbating inflammation and cellular demise in different diseases. Therefore, a thorough review on the significance of HMGB1 in drug-induced organic damage is highly important for the advancement of pharmaceuticals, ensuring their effectiveness and safety in treating inflammation as well as immune-related diseases. In this review, we initially outline the characteristics and functions of HMGB1, emphasizing their relevance in disease pathology. Then, we comprehensively summarize the prospect of HMGB1 as a promising therapeutic target for treating drug-induced toxicity. Lastly, we discuss major challenges and propose potential avenues for advancing the development of HMGB1-based therapeutics.
药物诱导的有机损伤包含各种复杂的机制，其中高迁移率族蛋白 B1（HMGB1）作为关键枢纽基因，发挥着重要作用。HMGB1 在核内和细胞外环境中的调节功能相互关联。HMGB1 对包括细胞存活、炎症调节和免疫反应在内的关键生物学过程具有重要的调节作用。在这些过程中，HMGB1 可以从细胞中外泌释放，作为一种促炎细胞因子发挥作用。HMGB1 与多种细胞膜受体相互作用，主要是 Toll 样受体（TLR）和晚期糖基化终产物受体（RAGE），以刺激免疫细胞并引发炎症反应。HMGB1 的过度或不受控制的释放会导致炎症反应加剧和细胞死亡，引发炎症损伤或加重不同疾病中的炎症和细胞死亡。因此，深入研究 HMGB1 在药物诱导的有机损伤中的意义对于推进药物学的发展非常重要，这可以确保药物在治疗炎症和免疫相关疾病方面的有效性和安全性。在这篇综述中，我们首先概述了 HMGB1 的特征和功能，强调了它们在疾病发病机制中的相关性。然后，我们全面总结了 HMGB1 作为治疗药物诱导毒性的有前途的治疗靶点的前景。最后，我们讨论了主要的挑战，并提出了推进基于 HMGB1 的治疗方法发展的潜在途径。
