Downregulated microRNA‐27b attenuates lipopolysaccharide‐induced acute lung injury via activation of NF‐E2‐related factor 2 and inhibition of nuclear factor κB signaling pathway

Abstract

Acute lung injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema, and respiratory failure. Lipopolysaccharide (LPS) is a leading cause for ALI and when administered to a mouse it induces a lung phenotype exhibiting some of the clinical characteristics of human ALI.This study focused on investigating whether microRNA-27b (miR-27b) affects ALI in a mouse model established by LPS-induction and to further explore the underlying mechanism. After model establishment, the mice were treated with miR-27b agomir, miR-27b antagomir, or D-ribofuranosylbenzimidazole (an inhibitor of nuclear factor-E2-related factor 2 [Nrf2]) to determine levels of miR-27b, Nrf2, nuclear factor kappa-light-chain-enhancer of activated B cells nuclear factor κB (NF-κB), p-NF-κB, and heme oxygenase-1 (HO-1). The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) were determined.The results of luciferase activity suggested that Nrf2 was a target gene of miR-27b. It was indicated that the Nrf2 level decreased in lung tissues from ALI mice. The downregulation of miR-27b decreased the levels of IL-1β, IL-6, and TNF-α in BALF of ALI mice. Downregulated miR-27b increased Nrf2 level, thus enhancing HO-1 level along with reduction of NF-κB level as well as the extent of NF-κB phosphorylation in the lung tissues of the transfected mice. Pathological changes were ameliorated in LPS-reduced mice elicited by miR-27b inhibition. The results of this study demonstrate that downregulated miR-27b couldenhance Nrf2 and HO-1 expressions, inhibit NF-κB signaling pathway, which exerts a protective effect on LPS-induced ALI in mice.

lncRNA CASC2 inhibits lipopolysaccharide‑induced acute lung injury via miR‑27b/TAB2 axis

“…in the present study, the expression of mir-27b was higher in the lPS-treated a549 group compared with that in the non-treated group. additionally, it was found that mir-27b overexpression reversed the protective effects of caSc2 expression on lPS-stimulated a549 cells, and the role of mir-27b in ali was consistent with the findings of a previous study (16).…”

“…However, there are very few studies focused on the role of miR-27b in ALI. Huang et al (16) reported that mir-27b facilitated lPS-induced ali via nrf2 protein and the nF-κB signaling pathway. in the present study, the expression of mir-27b was higher in the lPS-treated a549 group compared with that in the non-treated group.…”

“…mirnas have been reported to participate in the initiation and progression of lung inflammation (15). Huang et al (16) demonstrated that mir-27b promoted lPS-induced ali by regulating nuclear factor erythroid 2-related factor 2 (nrf2) and nF-κB signaling. The present study aimed to elucidate the underlying mechanism of mir-27b in ali.…”

MicroRNA‑93 contributes to the suppression of lung inflammatory responses in LPS‑induced acute lung injury in mice via the TLR4/MyD88/NF‑κB signaling pathway

“…A number of studies have demonstrated the involvement of miRNAs in the regulation of the inflammatory response in ALI. Several miRNAs, such as miR-24 and miR-27b, have been shown to attenuate lung injury in vitro and in vivo (45,46). miR-93 has previously been reported to play an important role in inflammatory diseases.…”

Effects of AntagomiRs on Different Lung Diseases in Human, Cellular, and Animal Models

“…The PubMed database was searched between 1 January 2000 and 30 April 2019 under the following search strategy: (((antagomiR) OR (mirna antagonists) OR (mirna antagonist)) AND ((lung[MeSH Terms]) OR (“lung diseases”[MeSH Terms]))). In this analysis, we included original articles, published in English, whereas exclusion criteria included reviews, meta-analyses, single case reports, and studies published in a language other than English [3,7,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71].…”