Emerging role of HMGB1 in fibrotic diseases

Abstract

High-mobility group box 1 (HMGB1) is originally identified as a DNA-binding protein that functions as a structural co-factor critical for proper transcriptional regulation in somatic cells. Recent studies indicate that HMGB1 can be passively released from necrotic cells or actively secreted into the extracellular milieu under appropriate signal stimulation. Extracellular HMGB1 is a multifunctional cytokine that contributes to the process of infection, injury, inflammation, apoptosis, and immune responses by binding to specific cell-surface receptors. Recently, emerging studies indicate that HMGB1 is closely involved in fibrotic disorders including cystic fibrosis, liver fibrosis and pulmonary fibrosis, while HMGB1 signal inhibitions protect against the experimental models of fibrotic diseases. From a clinical perspective, HMGB1 represents a current challenge that can be exploited orchestrate reparative responses. This review focuses on the crucial role of HMGB1 in the pathogenesis of fibrotic diseases and inhibition of which may represent a promising clinical approach for treating tissue fibrosis.