The role of high mobility group box 1 (HMGB1) in the pathogenesis of kidney diseases

Abstract

High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases.

Keywords: Acute kidney injury; Antineutrophil cytoplasmic autoantibody-associated vasculitis; Chronic kidney disease; Clear cell renal cell carcinoma; Diabetic nephropathy; High mobility group box 1; Inflammation; Nephritis.

Graphical abstract

Figure 1

Interaction of extracellular HMGB1 released from inflammatory and necrotic cells with cell surface receptors. (a) HMGB1 binds to RAGE which induces nuclear transcription of NF-κB, leading to transcription and expression of target genes of cytokines and chemokines; (b) HMGB1 causes inflammation by interacting with TLR2/TLR4 through MyD88 dependent and independent pathways; (c) the heterocomplex formed by binding of HMGB1 and CXCL12 promotes the migration of monocytes and fibroblasts.