Therapeutic Potential of High Mobility Group Box-1 in Ischemic Injury and Tissue Regeneration
Therapeutic Potential of High Mobility Group Box-1 in Ischemic Injury and Tissue Regeneration
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DOI：
10.2174/157016111797484125
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Flex, Andrea
中科院分区：
文献类型：
--
作者：
Biscetti, Federico;Ghirlanda, Giovanni;Flex, Andrea
HMGB1 （High-mobility group box-1）是一种核蛋白，当坏死细胞和炎症细胞释放到细胞外环境时，其作用是细胞因子，参与炎症反应和组织修复。这种蛋白在细胞坏死过程中被几乎所有有核的细胞被动释放，但也被免疫细胞如巨噬细胞和单核细胞主动分泌。这种细胞因子在介导局部和全身对几种刺激的反应中起关键作用，可能具有治疗相关性。事实上，将血管相关干细胞注射到营养不良小鼠的循环系统中，通过核因子κ b依赖机制响应HMGB1信号迁移到组织损伤部位。此外，内源性HMGB1在小鼠心肌梗死模型中促进血管生成，恢复心功能，心肌梗死后外源性HMGB1通过心肌细胞再生导致左心室功能恢复。最后，最近的研究表明，内源性HMGB1对糖尿病小鼠缺血诱导的血管生成至关重要，HMGB1蛋白通过vegf依赖的方式增强糖尿病小鼠缺血后肢的侧支血流量。这种蛋白质的作用机制是复杂的，不为人所知或定义。本综述的目的是评价HMGB1在组织再生作用方面的数据，旨在为缺血性和退行性疾病患者的管理提供实用的参考。
High-mobility group box-1 (HMGB1) is a nuclear protein that acts as a cytokine when released into the extracellular milieu by necrotic and inflammatory cells, and is involved in inflammatory responses and tissue repair. This protein is released passively during cellular necrosis by almost all cells that have a nucleus, but is also actively secreted by immune cells such as macrophages and monocytes. This cytokine plays a key role in mediating the local and systemic responses to several stimuli and might have therapeutic relevance. Indeed, vessel-associated stem cells, injected into the general circulation of dystrophic mice, migrate to sites of tissue damage in response to the HMGB1 signal, by a nuclear factor-kappa B-dependent mechanism. Moreover, endogenous HMGB1 enhances angiogenesis and restores cardiac function in a murine model of myocardial infarction, and the exogenous administration of HMGB1 after myocardial infarction leads to the recovery of left ventricular function through the regeneration of cardiomyocytes. Finally, recent findings show that endogenous HMGB1 is crucial for ischemia-induced angiogenesis in diabetic mice and that HMGB1 protein administration enhances collateral blood flow in the ischemic hind limbs of diabetic mice through a VEGF-dependent manner. The mechanisms of action of this protein are complex and are not well known or defined. The objective of this review is to evaluate the data regarding the tissue regeneration effects of HMGB1, with the aim of providing practical considerations about this topic for the management of subjects affected by ischemic and degenerative diseases.