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Role of High-Mobility Group Box-1 in Liver Pathogenesis

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5314;
Received: 4 October 2019 / Revised: 16 October 2019 / Accepted: 23 October 2019 / Published: 25 October 2019
(This article belongs to the Special Issue HMG Proteins in Development and Disease)
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. View Full-Text
Keywords: HMGB1; autophagy; inflammation; fibrosis; ductular reaction; tumor; NAFLD; ALD; DILI HMGB1; autophagy; inflammation; fibrosis; ductular reaction; tumor; NAFLD; ALD; DILI
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MDPI and ACS Style

Khambu, B.; Yan, S.; Huda, N.; Yin, X.-M. Role of High-Mobility Group Box-1 in Liver Pathogenesis. Int. J. Mol. Sci. 2019, 20, 5314.

AMA Style

Khambu B, Yan S, Huda N, Yin X-M. Role of High-Mobility Group Box-1 in Liver Pathogenesis. International Journal of Molecular Sciences. 2019; 20(21):5314.

Chicago/Turabian Style

Khambu, Bilon, Shengmin Yan, Nazmul Huda, and Xiao-Ming Yin. 2019. "Role of High-Mobility Group Box-1 in Liver Pathogenesis" International Journal of Molecular Sciences 20, no. 21: 5314.

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