Role of high-mobility group box-1 in liver pathogenesis

Bilon Khambu, Shengmin Yan, Nazmul Huda, Xiao Ming Yin

Research output: Contribution to journalReview article

Abstract

High-mobility group box 1 (HMGB1) is a highly abundant DNA-binding protein that can relocate to the cytosol or undergo extracellular release during cellular stress or death. HMGB1 has a functional versatility depending on its cellular location. While intracellular HMGB1 is important for DNA structure maintenance, gene expression, and autophagy induction, extracellular HMGB1 acts as a damage-associated molecular pattern (DAMP) molecule to alert the host of damage by triggering immune responses. The biological function of HMGB1 is mediated by multiple receptors, including the receptor for advanced glycation end products (RAGE) and Toll-like receptors (TLRs), which are expressed in different hepatic cells. Activation of HMGB1 and downstream signaling pathways are contributing factors in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and drug-induced liver injury (DILI), each of which involves sterile inflammation, liver fibrosis, ductular reaction, and hepatic tumorigenesis. In this review, we will discuss the critical role of HMGB1 in these pathogenic contexts and propose HMGB1 as a bona fide and targetable DAMP in the setting of common liver diseases.

Original languageEnglish (US)
Article number5314
JournalInternational journal of molecular sciences
Volume20
Issue number21
DOIs
StatePublished - Nov 1 2019

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Chemical and Drug Induced Liver Injury
pathogenesis
Alcoholic Liver Diseases
Toll-Like Receptors
Autophagy
DNA-Binding Proteins
liver
Liver Cirrhosis
Liver
Cytosol
boxes
Liver Diseases
Hepatocytes
Carcinogenesis
Maintenance
Inflammation
Gene Expression
DNA
damage
Gene expression

Keywords

  • ALD
  • Autophagy
  • DILI
  • Ductular reaction
  • Fibrosis
  • HMGB1
  • Inflammation
  • NAFLD
  • Tumor

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Role of high-mobility group box-1 in liver pathogenesis. / Khambu, Bilon; Yan, Shengmin; Huda, Nazmul; Yin, Xiao Ming.

In: International journal of molecular sciences, Vol. 20, No. 21, 5314, 01.11.2019.

Research output: Contribution to journalReview article

Khambu, Bilon ; Yan, Shengmin ; Huda, Nazmul ; Yin, Xiao Ming. / Role of high-mobility group box-1 in liver pathogenesis. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 21.
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