Role of high-mobility group box-1 protein in disruption of vascular barriers and regulation of leukocyte-endothelial interactions.
High-mobility group box-1 protein (HMGB1) is a highly conserved non-histone DNA-binding protein present in the nuclei and cytoplasm of nearly all cell types. The results from recent research provide evidence that HMGB1 is secreted into the extracellular milieu and acts as a pro-inflammatory cytokine and exhibits angiogenic effects to fire the immunological response against the pathological effects. Recently, a great deal of evidence has indicated the critical importance of HMGB1 in mediating vascular barriers dysfunction by modulating the expression of adhesion molecules, such as intercellular adhesion molecule-1, vascular cell adhesion protein 1 and E-selectin on the surface of endothelial cells. Such process promotes the adhesion and migration of leukocytes across the endothelium, leading to breakdown of vascular barriers (blood-brain barrier and blood-retinal barrier) via modulating the expression, content, phosphorylation, and distribution of tight junction proteins. Therefore, here we give an abridged review to understand the mechanistic link between HMGB1 and vascular barriers dysfunction, including interaction with cell-surface receptors and intracellular signaling pathways.
a Department of Ophthalmology , College of Medicine, King Saud University, and Dr. Nasser Al-Rasheed Research Chair in Ophthalmology , Riyadh , Saudi Arabia.
Mohd Imtiaz
MI
Nawaz
a Department of Ophthalmology , College of Medicine, King Saud University, and Dr. Nasser Al-Rasheed Research Chair in Ophthalmology , Riyadh , Saudi Arabia.
Ghulam
G
Mohammad
D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D001808:Blood Vessels / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D018390:Gene Targeting; D024243:HMGB1 Protein / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007962:Leukocytes / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D015398:Signal Transduction
D057134:Antibodies, Neutralizing; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products
High-mobility group box-1; inflammation; leukocyte adhesion; signalling pathways; vascular barrier