The role of ubiquitination in microbial infection induced endothelial dysfunction: potential therapeutic targets for sepsis

ABSTRACT

Introduction

The ubiquitin system is an evolutionarily conserved and universal means of protein modification that regulates many essential cellular processes. Endothelial dysfunction plays a critical role in the pathophysiology of sepsis and organ failure. However, the mechanisms underlying the ubiquitination-mediated regulation on endothelial dysfunction are not fully understood.

Areas covered

Here we review the advances in basic and clinical research for relevant papers in PubMed database. We attempt to provide an updated overview of diverse ubiquitination events in endothelial cells, discussing the fundamental role of ubiquitination mediated regulations involving in endothelial dysfunction to provide potential therapeutic targets for sepsis.

Expert opinion

The central event underlying sepsis syndrome is the overwhelming host inflammatory response to the pathogen infection, leading to endothelial dysfunction. As the key components of the ubiquitin system, E3 ligases are at the center stage of the battle between host and microbial pathogens. Such a variety of ubiquitination regulates a multitude of cellular regulatory processes, including signal transduction, autophagy, inflammasome activation, redox reaction and immune response and so forth. In this review, we discuss the many mechanisms of ubiquitination-mediated regulation with a focus on those that modulate endothelial function to provide potential therapeutic targets for the management of sepsis.

KEYWORDS:

• Sepsis
• endothelial cells
• pathogen infection
• ubiquitination
• signal transduction

Article highlights

• Sepsis is a severe endothelial dysfunction syndrome caused by a dysregulated host response to microbial infection

• The ubiquitin system is a double-edged sword that is often exploited during pathogen invasion

• Ubiquitination events form a sophisticated and versatile regulatory system that can profoundly affect endothelial function

• Ubiquitination is involved in the signal transduction pathways of the pattern recognition receptors in the endothelial cells

• Ubiquitination regulates endothelial autophagy

• Ubiquitination mediates redox reactions in endothelial cells

• Ubiquitination modulates inflammasome activation in endothelial cells

• Ubiquitination is involved in immune injuries to endothelial cells

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Natural Science Foundation of Hubei Province under Grant 2022CFB148.