Dataset Information

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

ABSTRACT: Acute lung injury (ALI) is a severe inflammatory lung disease with a rapid onset. The anti?inflammatory functions of microRNA?93 (miRNA/miR?93) have been described in various types of tissue injury and disease. However, the biological role of miR?93 and its molecular mechanisms underlying the initiation and progression of ALI have not yet been reported, at least to the best of our knowledge. The present study aimed to investigate the regulatory effects exerted by miR?93 in ALI. Using an in vivo murine model of ALI induced by lipopolysaccharide (LPS), miR?93 expression was found to be downregulated in the lung tissues and bronchoalveolar lavage fluid (BALF) compared with the control group. Following agomiR?93 injection, it was observed that agomiR?93 attenuated lung injury, as evidenced by decreased lung permeability, a reduced lung wet/dry weight ratio and an increased survival rate of the mice. Concomitantly, agomiR?93 significantly reduced LPS?induced the interleukin (IL)?6, IL?1?, and tumor necrosis factor (TNF)?? levels in BALF. Of note, Toll?like receptor 4 (TLR4), an upstream regulator of the nuclear factor (NF)??B signaling pathway, was directly suppressed by miR?93 in RAW 264.7 cells. Importantly, agomiR?93 induced a significant suppression of the TLR4/myeloid differentiation primary response 88 (MyD88)/NF??B signaling pathway, as demonstrated by the downregulation of MyD88, and the phosphorylation of I?B?? and p65 in the lung tissues of mice with ALI. Taken together, the findings of the present study indicate that miR?93 attenutes LPS?induced lung injury by regulating the TLR4/MyD88/NF??B signaling pathway, suggesting that miR?93 may prove to be a potential therapeutic target for ALI.

SUBMITTER: Gao H

PROVIDER: S-EPMC7307825 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Gao Hu H Xiao Dongqiong D Gao Linbo L Li Xihong X

International journal of molecular medicine 20200519 2

Acute lung injury (ALI) is a severe inflammatory lung disease with a rapid onset. The anti‑inflammatory functions of microRNA‑93 (miRNA/miR‑93) have been described in various types of tissue injury and disease. However, the biological role of miR‑93 and its molecular mechanisms underlying the initiation and progression of ALI have not yet been reported, at least to the best of our knowledge. The present study aimed to investigate the regulatory effects exerted by miR‑93 in ALI. Using an in vivo ...[more]

PMID: 32468034

Similar Datasets

Project description:BackgroundIt is widely accepted that inflammation may contribute to cognitive impairment in patients with vascular dementia (VD). Our prior clinical researches have reported that acupuncture can alleviate cognitive function in VD, but the underlying mechanisms are still unclear. The purpose of this research was to explore whether acupuncture alleviates cognitive impairment by suppressing the microRNA-93- (miR-93-) mediated Toll-like receptor (TLR) signaling pathway, which triggers inflammatory responses in the central nervous system.MethodsVD was established by permanent bilateral common carotid artery occlusion in male Wistar rats. Three days after operation, the rats began daily treatment with acupuncture for two weeks. The levels of miR-93, Toll-like receptors (TLR2 and TLR4), intracellular signaling molecules (myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB)), and inflammatory cytokines were subsequently detected. TLR4 colocalized with neurons, microglia, and astrocytes in the hippocampus was evaluated. Neuroinflammation and cognitive function were determined after intracerebroventricular injection of TLR4 antagonist TAK-242 or agonist lipopolysaccharide (LPS) with or without acupuncture.ResultsWe found that acupuncture notably repressed the expression of inflammatory cytokines in the hippocampus and plasma of VD rats. The expression of TLR4, but not TLR2, was markedly downregulated by acupuncture, accompanied by a decrease in miR-93 and MyD88/NF-κB signaling pathway activation. The overexpression of TLR4 in microglia, but not in astrocytes and neurons, was reversed by acupuncture. Furthermore, intracerebroventricular injection of TAK-242 had similar effects to acupuncture on inflammation and cognitive function, while LPS injection abolished the beneficial effects of acupuncture.ConclusionsTaken together, these findings provide evidence that acupuncture attenuates cognitive impairment associated with inflammation through inhibition of the miR-93-mediated TLR4/MyD88/NF-κB signaling pathway in experimental VD. Acupuncture serves as a promising alternative therapy and may be an underlying TLR4 inhibitor for the treatment of VD.

Dataset Information

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

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets