LncRNA MEG3 Involved in NiO NPs-Induced Pulmonary Fibrosis via Regulating TGF-β1-Mediated PI3K/AKT Pathway

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The lung inflammatory damage could result from the nickel oxide nanoparticles (NiO NPs), in which the underlying mechanism is still unclear. This article explored the roles of long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) and p38 mitogen activated protein kinases (p38 MAPK) pathway in pulmonary inflammatory injury induced by NiO NPs. Wistar rats were treated with NiO NPs suspensions (0.015, 0.06, and 0.24 mg/kg) by intratracheal instillation twice‐weekly for 9 weeks. Meanwhile, A549 cells were treated with NiO NPs suspensions (25, 50, and 100 μg/ml) for 24 h. It can be concluded that the NiO NPs did trigger pulmonary inflammatory damage, which was confirmed by the histopathological examination, abnormal changes of inflammatory cells and inflammatory cytokines (IL‐1β, IL‐6, TGF‐β1, TNF‐α, IFN‐γ, IL‐10, CXCL‐1 and CXCL‐2) in bronchoalveolar lavage fluid (BALF), pulmonary tissue and cell culture supernatant. Furthermore, NiO NPs activated the p38 MAPK pathway and downregulated MEG3 in vivo and in vitro. However, p38 MAPK pathway inhibitor (10 μM SB203580) reversed the alterations in the expression levels of inflammatory cytokines induced by NiO NPs. Meanwhile, over‐expressed MEG3 significantly suppressed NiO NPs‐induced p38 MAPK pathway activation and inflammatory cytokines changes. Overall, the above results proved that over‐expression of lncRNA MEG3 reduced NiO NPs‐induced inflammatory damage by preventing the activation of p38 MAPK pathway.

Section: Resultsmentioning

confidence: 87%

Section: Discuissionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Section: Over-expression Of Lncrna Meg3 Inhibited the Activation Of P...mentioning

confidence: 99%

Section: Discuissionmentioning

confidence: 99%

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LncRNA MEG3amelioratesNiOnanoparticles‐induced pulmonary inflammatory damage via suppressing the p38 mitogen activated protein kinases pathway

Chang

Gao

Gong

et al. 2022

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LncRNA MEG3 restrained pulmonary fibrosis induced by NiO NPs via regulating hedgehog signaling pathway‐mediated autophagy

Gao

Chang

Zheng

et al. 2021

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Long noncoding RNA maternally expressed gene 3 (lncRNA MEG3) was downregulated in pulmonary fibrosis of rats induced by Nickel oxide nanoparticles (NiO NPs), while the downstream regulatory mechanisms of MEG3 remain unclear. This study aimed to investigate the relationship among MEG3, Hedgehog (Hh) signaling pathway and autophagy in pulmonary fibrosis caused by NiO NPs. The pulmonary fibrosis model in rats was constructed by intratracheal instillation of 0.015, 0.06, and 0.24 mg/kg NiO NPs twice a week for 9 weeks. Collagen deposition model was established by treating A549 cells with 25, 50, and 100 μg/mL NiO NPs for 24 h. Our results indicated that NiO NPs activated Hh pathway, down-regulated the expression of MEG3, and reduced autophagy activity in vivo and in vitro. Meanwhile, the autophagy process was promoted by Hh pathway inhibitor (CDG-0449), while the collagen formation in A549 cells was reduced by autophagy activator (Rapamycin). Furthermore, the overexpressed MEG3 inhibited the activation of Hh pathway, resulting in autophagy activity enhancement along with collagen formation reduction. In summary, lncRNA MEG3 can restrain pulmonary fibrosis induced by NiO NPs via regulating hedgehog signaling pathway-mediated autophagy, which may serve as a potential therapeutic strategy for pulmonary fibrosis.

LncRNA AP000487.1 regulates PRKCB DNA methylation‐mediated TLR4/MyD88/NF‐κB pathway in Nano NiO‐induced collagen formation in BEAS‐2B cells

Zheng,

Wang,

et al. 2023

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Nickel oxide nanoparticles (Nano NiO) have been shown to cause pulmonary fibrosis; But, the underlying epigenetic mechanisms remain poorly understood. In this study, we aimed to investigate the role of lncRNA AP000487.1 in regulating PRKCB DNA methylation and the Toll‐like receptor 4 (TLR4)/ Myeloid differentiation primary response 88 (MyD88)/ Nuclear factor kappa‐B (NF‐κB) pathway in Nano NiO‐induced collagen formation. We found that lncRNA AP000487.1 was able to bind to the promoter region of the PRKCB gene by Chromosomal RNA pull‐down experiments (Ch‐RNA pull‐down). Moreover, Nano NiO exposure led to down‐regulation of lncRNA AP000487.1 expression and PRKCB DNA methylation, resulting in up‐regulation of PRKCB expression, activation of the TLR4/MyD88/NF‐κB pathway, and increased collagen formation in BEAS‐2B cells. Conversely, overexpression of lncRNA AP000487.1 restored PRKCB expression, reduced its hypomethylation and attenuated TLR4/MyD88/NF‐κB pathway activation and collagen formation. Furthermore, treatment with the DNA methylation inhibitor, decitabine, alleviated Nano NiO‐induced PRKCB2 expression, TLR4/MyD88/NF‐κB pathway activation, and collagen formation. Additionally, using PRKCB2 overexpression plasmid, PRKCB2 siRNA, and PRKCB2 protein inhibitor LY317615 influenced NF‐κB pathway activity and collagen formation. Finally, TLR4 inhibitor (TAK‐242) restrained Nano NiO‐induced MyD88/NF‐κB pathway activation and excessive collagen formation. In summary, we demonstrated that the down‐regulated lncRNA AP000487.1 could cause PRKCB hypomethylation and increased expression, resulting in NF‐κB pathway activation and collagen formation in Nano NiO‐induced BEAS‐2B cells. This is the first study to reveal the role of lncRNA AP000487.1 in regulating collagen formation in Nano NiO‐exposed BEAS‐2B cells. Our study identified that lncRNA AP000487.1/PRKCB hypomethylation/NF‐κB pathway was a regulatory axis of BEAS‐2B cells collagen excessive formation. Our findings indicate that lncRNA AP000487.1 and PRKCB DNA methylation may function as biomarkers or potential targets in response to Nano NiO exposure.