Long Non-coding RNA TUG1 Modulates Expression of Elastin to Relieve Bronchopulmonary Dysplasia via Sponging miR-29a-3p.

Qinghua Zhong,Kun Liang,Li Wang,Zhiye Qi,Jiang Duan,Jia Cao,Caiying Zhang

doi:10.3389/fped.2020.573099

Abstract

Objective: Multiple studies have highlighted that long non-coding RNAs (lncRNAs) may exert paramount roles in relieving bronchopulmonary dysplasia (BPD). The aim of our investigation is to probe the role and mechanism of lncRNA taurine upregulated gene 1 (TUG1) in BPD.Methods: The current mouse model of BPD was simulated by induction of hyperoxia, and hyperoxia-induced mouse type II alveolar epithelial (MLE-12) (MLE-12) cells were established as a cellular model. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine relative expressions of TUG1, miR-29a-3p, and elastin (ELN). We assessed cell apoptosis by TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. Western blot was used for detection of apoptosis-related proteins. Moreover, cell viability was tested by cell counting kit-8 (CCK-8) assay. Inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter (DLR) assay was employed to confirm relationship between genes.Results: Upregulation of miR-29a-3p was found in lung tissues of BPD mice compared with lung tissues without BPD, while downregulations of TUG1 and ELN were discovered in BPD tissues in comparison with tissues without BPD. Increasing TUG1 was shown to alleviate lung injury of BPD mice and promote proliferation of hyperoxia-induced MLE-12 cells. Meanwhile, TUG1 inhibited inflammatory response and cell apoptosis in lung tissues of BPD mice and hyperoxia-induced MLE-12 cells. miR-29a-3p was targeted by TUG1 and negatively modulated by TUG1. ELN was inversely regulated by miR-29a-3p. Meantime, suppressive effects of TUG1 on apoptosis and inflammation were reversed by decreasing ELN or increasing miR-29a-3p in hyperoxia-induced MLE-12 cells.Conclusion: lncRNA TUG1 relieved BPD through regulating the miR-29a-3p/ELN axis, which provided a therapeutic option to prevent or ameliorate BPD.

Highlights

Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, is the most common respiratory disorder among infants born extremely preterm
taurine upregulated gene 1 (TUG1) inhibited inflammatory response and cell apoptosis in lung tissues of BPD mice and hyperoxia-induced MLE-12 cells. miR-29a-3p was targeted by TUG1 and negatively modulated by TUG1
The result of Quantitative real-time polymerase chain reaction (qRT-PCR) showed that TUG1 was markedly downregulated in the hyperoxia group relative to that in the blank group (P < 0.01) (Figure 1A), and relative expression of TUG1 in the hyperoxia-TUG1 group was increased compared with the hyperoxia-negative control (NC) group (P < 0.01) (Figure 1A)

Summary

Introduction

Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, is the most common respiratory disorder among infants born extremely preterm. The pathogenesis of BPD is multifactorial [1]. Apart from postnatal determinants of lung injury and low gestational age, adverse antenatal factors, such as gestational hypertensive disorders, maternal obesity, and gestational diabetes, lead to the pathological and clinical features of BPD [2,3,4]. There are many studies to support several therapeutic strategies, including antenatal glucocorticoids, surfactant therapy, interleukin-1 receptor antagonist, and microbiome [5, 6]. Despite intensifying efforts to manage BPD, BPD incidence and mortality of preterm neonates still pose a great challenge for us [7]. Raising novel prospects of therapy is essential for contributing to the development of BPD treatment

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Results

Conclusion