The Emerging Roles of Tripartite Motif Proteins (TRIMs) in Acute Lung Injury.

Yingjie Huang,Yong Li,Xuekang Zhang,Yue Xiao,Xuan Huang

doi:10.1155/2021/1007126

Abstract

Acute lung injury (ALI) is an inflammatory disorder of the lung that causes high mortality and lacks any pharmacological intervention. Ubiquitination plays a critical role in the pathogenesis of ALI as it regulates the alveolocapillary barrier and the inflammatory response. Tripartite motif (TRIM) proteins are one of the subfamilies of the RING-type E3 ubiquitin ligases, which contains more than 80 distinct members in humans involved in a broad range of biological processes including antivirus innate immunity, development, and tumorigenesis. Recently, some studies have shown that several members of TRIM family proteins play important regulatory roles in inflammation and ALI. Herein, we integrate emerging evidence regarding the roles of TRIMs in ALI. Articles were selected from the searches of PubMed database that had the terms “acute lung injury,” “ubiquitin ligases,” “tripartite motif protein,” “inflammation,” and “ubiquitination” using both MeSH terms and keywords. Better understanding of these mechanisms may ultimately lead to novel therapeutic approaches by targeting TRIMs for ALI treatment.

Highlights

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various direct or indirect injuries including sepsis syndrome, ischemia-reperfusion, pneumonia, and mechanical ventilation, which leads to the destruction of the barrier of alveolar epithelial cells and capillary endothelial cells, resulting in overinfiltration of inflammatory cells and diffuse pulmonary interstitial and alveolar edema [1]
We recently found that TRIM65 selectively targeted vascular cell adhesion molecule 1 (VCAM-1) and promoted its ubiquitination and degradation, by which it critically controlled the duration and magnitude of pulmonary inflammation in ALI [45]
TRIM8 has been revealed to play an important role in acute lung injury, precise regulatory mechanisms such as whether it depends on the activity of E3 ubiquitin ligase and its specific target proteins need to be further clarified

Summary

Introduction

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various direct (pulmonary) or indirect (extrapulmonary) injuries including sepsis syndrome, ischemia-reperfusion, pneumonia, and mechanical ventilation, which leads to the destruction of the barrier of alveolar epithelial cells and capillary endothelial cells, resulting in overinfiltration of inflammatory cells and diffuse pulmonary interstitial and alveolar edema [1]. There is still no effective pharmaceutical intervention for ALI; mechanical ventilation is the main approach to prevent respiratory failure and, combined with intensive care support, could improve health condition [10]. Emerging evidence points out to the ubiquitination which functions as an important regulator in the pathobiology of ALI since it regulates the proteins evolved in the modulation of the alveolocapillary barrier and inflammatory response, opening a highly promising research field for the treatment of lung diseases [14]

Ubiquitination in ALI

TRIMs in ALI

Conclusions