Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

Qingsong Sun,Weiqin Wu,Man Luo,Zhiwei Gao,Hongmei Zhao,Xiang Han

doi:10.1186/s12890-021-01589-1

Abstract

BackgroundAcute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI.MethodsWe used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI.ResultTLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis.ConclusionOIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

Highlights

Acute lung injury (ALI), a severe respiratory disorder, is characterized by heterogeneous pathologic factors [1, 2]
OIP5-AS1 promotes ALI by regulating the miR-26a-5p/toll-like receptor 4 (TLR4) axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI
TLR4 is upregulated in ALI mice and LPS‐treated cells To investigate the potential role of TLR4 in lung injury, the ALI mice model was established via intratracheally instilling with LPS

Summary

Introduction

Acute lung injury (ALI), a severe respiratory disorder, is characterized by heterogeneous pathologic factors [1, 2]. The knockdown of lncRNA X-inactive specific transcript mitigates primary graft dysfunction by sponging miR-21 and targeting IL12A following lung transplantation [17]. LncRNA OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been reported to involve in pathogenesis of diverse diseases including tumors [19, 20], myocardial ischemia/reperfusion injury [21], and osteoarthritis [22]. OIP5-AS1 was revealed to regulate cell injury and inflammatory response in atherosclerosis and rheumatoid arthritis [23, 24]. Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI

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