CircRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury.

Jiang Zhu,Yingying Liao,Qiaohong Bai,Yong Zhou,Fukuan Zhong,Futao Chen,Yang Yang,Lifeng Cao

doi:10.1515/med-2022-0417

Jiang Zhu, Yingying Liao + Show 6 more

Open Access

https://doi.org/10.1515/med-2022-0417

Copy DOI

Abstract

Acute lung injury (ALI) is a respiratory disorder characterized by acute respiratory failure. circRNA mus musculus (mmu)-circ_0001679 was reported overexpressed in septic mouse models of ALI. Here the function of circ_0001679 in sepsis-induced ALI was investigated. In vitro models and animal models with ALI were, respectively, established in mouse lung epithelial (MLE)-12 cells and C57BL/6 mice. Pulmonary specimens were harvested for examination of the pathological changes. The pulmonary permeability was examined by wet-dry weight (W/D) ratio and lung permeability index. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the bronchoalveolar lavage fluid (BALF), the lung tissues, and the supernatant of MLE-12 cells were measured by enzyme linked immunosorbent assay . Apoptosis was determined by flow cytometry. Bioinformatics analysis and luciferase reporter assay were used to assess the interactions between genes. We found that circ_0001679 was overexpressed in lipopolysaccharide (LPS)-stimulated MLE-12 cells. circ_0001679 knockdown suppressed apoptosis and proinflammatory cytokine production induced by LPS. Moreover, circ_0001679 bound to mmu-miR-338-3p and miR-338-3p targeted dual-specificity phosphatases 16 (DUSP16). DUSP16 overexpression reversed the effect of circ_0001679 knockdown in LPS-stimulated MLE-12 cells. Furthermore, circ_0001679 knockdown attenuated lung pathological changes, reduced pulmonary microvascular permeability, and suppressed inflammation in ALI mice. Overall, circ_0001679 knockdown inhibits sepsis-induced ALI progression through the miR-338-3p/DUSP16 axis.

Highlights

Sepsis is a complex inflammatory disorder induced by bacterial infection, resulting in multi-organ dysfunction syndrome, including lung, kidney, liver, and cardiovascular system [1,2]
All data from three independent experiments are shown as the mean value ± standard deviation (SD)
The correlation between gene expressions in mouse lung tissues was analyzed by Pearson correlation analysis

Summary

Introduction

Sepsis is a complex inflammatory disorder induced by bacterial infection, resulting in multi-organ dysfunction syndrome, including lung, kidney, liver, and cardiovascular system [1,2]. Acute lung injury (ALI) characterized by overwhelming hyperinflammation in lung is a severe complication of sepsis, with a high incidence and mortality [3]. 50% of patients with sepsis develop ALI [4,5]. Despite improved therapeutic strategies in clinical treatment for ALI, it is still a major challenge, with a mortality rate as high as 35–40% [6]. It has been reported that sepsis-induced ALI is related to alveolar epithelial cell apoptosis, abnormal inflammatory response in the lung, and excessive oxidative stress [7]. Inflammatory mediators and cytokines have been considered to play key roles in initiating, augmenting, and maintaining sepsis-induced ALI [8]. Studies show that the administration of lipopolysaccharide (LPS) has been widely used to establish sepsis-associated lung injury models [9]

Methods

Results

Conclusion