HMGB1: a double-edged sword and therapeutic target in the female reproductive system

Front Immunol. 2023 Aug 18:14:1238785. doi: 10.3389/fimmu.2023.1238785. eCollection 2023.

Abstract

HMGB1 that belongs to the High Mobility Group-box superfamily, is a nonhistone chromatin associated transcription factor. It is present in the nucleus of eukaryotes and can be actively secreted or passively released by kinds of cells. HMGB1 is important for maintaining DNA structure by binding to DNA and histones, protecting it from damage. It also regulates the interaction between histones and DNA, affecting chromatin packaging, and can influence gene expression by promoting nucleosome sliding. And as a DAMP, HMGB1 binding to RAGE and TLRs activates NF-κB, which triggers the expression of downstream genes like IL-18, IL-1β, and TNF-α. HMGB1 is known to be involved in numerous physiological and pathological processes. Recent studies have demonstrated the significance of HMGB1 as DAMPs in the female reproductive system. These findings have shed light on the potential role of HMGB1 in the pathogenesis of diseases in female reproductive system and the possibilities of HMGB1-targeted therapies for treating them. Such therapies can help reduce inflammation and metabolic dysfunction and alleviate the symptoms of reproductive system diseases. Overall, the identification of HMGB1 as a key player in disease of the female reproductive system represents a significant breakthrough in our understanding of these conditions and presents exciting opportunities for the development of novel therapies.

Keywords: HMGB1; anti-HMGB1; female reproductive system diseases; inflammation; pregnancy complications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alarmins
  • Chromatin
  • Female
  • Genitalia, Female*
  • HMGB1 Protein*
  • Histones
  • Humans
  • Tumor Necrosis Factor-alpha

Substances

  • Alarmins
  • Chromatin
  • Histones
  • HMGB1 Protein
  • Tumor Necrosis Factor-alpha
  • HMGB1 protein, human

Grants and funding

This research was supported by the National Natural Sciences Foundation of China (No. 32000642), the Young and Middle-aged Doctors in Reproductive Medicine Research-Basic Research Projects (No. BJHPA-2022-SHZHYXZHQNYJ-JICH-003), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2019PT310002), the Research Fund of Anhui Institute of translational medicine (2021zhyx-B16).