Targeting HMGB1 for the treatment of sepsis and sepsis- induced organ injury
Chao Deng1,2,3,
Lin Zhao4,
Zhi Yang1,5,
Jia-jia Shang1,5,
Chang-yu Wang6,
Ming-zhi Shen7,
Shuai Jiang1,5,
Tian Li1,
Wen-cheng Di8,
Ying Chen9,
He Li1,5,
Ye-dong Cheng2,
Yang Yang1,5
1 Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, Xi’an 710021, China
2 Department of Orthopaedics, Huaian Medical District of Jingling Hospital, Medical School of Nanjing University, Huaian 213001, China
3 Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
4 Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China
5 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Life of Sciences, Northwest University, Xi’an 710021, China
6 Department of Cardiology, Xi’an No.3 Hospital, School of Life Sciences and Medicine, Northwest University, Xi’an 710021, China
7 Hainan Hospital of PLA General Hospital, The Second School of Clinical Medicine, Southern Medical University, Sanya 572013, China
8 National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen 518100, China
9 Department of Hematology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Correspondence to: Ye-dong Cheng: yedongcheng888@126.com, Yang Yang: yang200214yy@nwu.edu.cn,
DOI: 10.1038/s41401-021-00676-7
Received: 22 November 2020
Accepted: 1 April 2021
Advance online: 26 May 2021
Abstract
High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is present in almost all cells and regulates the activity of innate immune responses in both intracellular and extracellular settings. Current evidence suggests that HMGB1 plays a pivotal role in human pathological and pathophysiological processes such as the inflammatory response, immune reactions, cell migration, aging, and cell death. Sepsis is a systemic inflammatory response syndrome (SIRS) that occurs in hosts in response to microbial infections with a proven or suspected infectious etiology and is the leading cause of death in intensive care units worldwide, particularly in the aging population. Dysregulated systemic inflammation is a classic characteristic of sepsis, and suppression of HMGB1 may ameliorate inflammation and improve patient outcomes. Here, we focus on the latest breakthroughs regarding the roles of HMGB1 in sepsis and sepsis-related organ injury, the ways by which HMGB1 are released, and the signaling pathways and therapeutics associated with HMGB1. This review highlights recent advances related to HMGB1: the regulation of HMBG1 might be helpful for both basic research and drug development for the treatment of sepsis and sepsis-related organ injury.
Keywords:
high mobility group box 1; sepsis; LPS; inflammation; Toll-like receptor
