Therapeutic potential of high mobility group box-1 in ischemic injury and tissue regeneration.

Abstract:

: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-κB 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.

journal_name

Curr Vasc Pharmacol

authors

Biscetti F,Ghirlanda G,Flex A

doi

10.2174/157016111797484125

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

677-81

issue

6

eissn

1570-1611

issn

1875-6212

pii

BSP/CVP/E-Pub/0000169

journal_volume

9

pub_type

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