Lipopolysaccharide-Induced Acute Lung Injury Is Associated with Increased Ran-Binding Protein in Microtubule-Organizing Center (RanBPM) Molecule Expression and Mitochondria-Mediated Apoptosis Signaling Pathway in a Mouse Model

Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils (PMNs) participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis, which is related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as one of the primary target sites. However, it is still unclear whether HBP-binding protein receptors exist on the surface of ECs. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro study. We demonstrated that HBP bound to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. GST pull-down analysis reveals that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induced acute lung injury (ALI) and vascular leakage via activation of TGF-β/SMAD2/3 signaling pathway. Permeability assay suggests TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related ALI.

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Whole transcriptome analysis of the differential RNA profiles and associated competing endogenous RNA networks in LPS-induced acute lung injury (ALI)

PLoS ONE ◽

10.1371/journal.pone.0251359 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251359

Author(s):

Xiangnan Teng ◽

Jing Liao ◽

Lili Zhao ◽

Wei Dong ◽

Haiyi Xue ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Differential Expression ◽

Signaling Pathway ◽

High Throughput Sequencing ◽

Target Genes ◽

Biological Function ◽

Function Analysis ◽

Whole Transcriptome

Acute lung injury (ALI) is a serious inflammation disease usually arises alveolar epithelial membrane dysfunction and even causes death. Therefore, the aims of this study are to screen the differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs in ALI based on the high-throughput sequencing. The lipopolysaccharide (LPS)-induced ALI mouse model was established, the injury of ALI mouse model was evaluated through histological analysis with hemotoxylin and eosin (H & E) staining assay, dry/wet ratio, infiltrated-immune cells, ET-1 mRNA expression and released-proinflammation factors. Then, expression data of lncRNAs, circRNAs, miRNAs and mRNAs in ALI were acquired using whole-transcriptome sequencing. The differential expression of lncRNAs (DE lncRNAs), circRNAs (DE circRNAs), miRNAs (DE miRNAs) and mRNAs (DE mRNAs) were identified, and the lncRNA-miRNA-mRNA network and circRNA-miRNA-mRNA network were constructed, and the biological function of target genes were annotated based on bioinformatics analysis. In the present study, the LPS-induced ALI mouse model was successfully established. The biological analysis results showed that total 201 DE lncRNAs, 172 DE circRNAs, 62 DE miRNAs, and 3081 DE mRNAs were identified in ALI. The 182 lncRNA-miRNA-mRNA networks and 32 circRNA-miRNA-mRNA networks were constructed were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The biological function analysis indicated that TNF signaling pathway, chemokine signaling pathway and so on involved in ALI. In the present study, the differential expression coding and non-coding RNAs (ncRNAs) in ALI were identified, and their regulatory networks were constructed. There might provide the potential biomarkers and underlying mechanism for ALI diagnosis and treatment.

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Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury

Molecular Medicine Reports ◽

10.3892/mmr.2018.9427 ◽

2018 ◽

Cited By ~ 11

Author(s):

Dandan Li ◽

Weiying Ren ◽

Zhilong Jiang ◽

Lei Zhu

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Signaling Pathway ◽

P38 Mapk ◽

Nlrp3 Inflammasome ◽

Mapk Signaling ◽

Mapk Signaling Pathway

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Faculty Opinions recommendation of Substance P upregulates cyclooxygenase-2 and prostaglandin E metabolite by activating ERK1/2 and NF-kappaB in a mouse model of burn-induced remote acute lung injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.6913958.7104054 ◽

2010 ◽

Author(s):

Steven D Douglas

Keyword(s):

Acute Lung Injury ◽

Substance P ◽

Lung Injury ◽

Mouse Model ◽

Cyclooxygenase 2 ◽

Prostaglandin E ◽

Nf Kappab

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Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:176-182 ◽

2019 ◽

Vol 18 (2) ◽

pp. 176-182

Author(s):

Chen Weiyan ◽

Deng Wujian ◽

Chen Songwei

Keyword(s):

Acute Lung Injury ◽

B Cells ◽

Lung Injury ◽

Signaling Pathway ◽

Light Chain ◽

Cecal Ligation ◽

Nuclear Factor ◽

Kappa Light Chain ◽

Cecal Ligation And Puncture ◽

Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

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Long Non-Coding RNA MEG3/microRNA-7b/NLR Pyrin Domain Containing 3 Axis Modulates Lipopolysaccharide-Induced Acute Lung Injury in a Mouse Model

SSRN Electronic Journal ◽

10.2139/ssrn.3405572 ◽

2019 ◽

Author(s):

Handi Liao ◽

Suning Zhang ◽

Jianou Qiao

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Pyrin Domain ◽

Non Coding Rna ◽

Long Non Coding Rna

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Impaired airway epithelial barrier integrity was mediated by PI3Kδ in a mouse model of lipopolysaccharide-induced acute lung injury

International Immunopharmacology ◽

10.1016/j.intimp.2021.107570 ◽

2021 ◽

Vol 95 ◽

pp. 107570

Author(s):

Lihong Yao ◽

Ying Tang ◽

Junjie Chen ◽

Jiahui Li ◽

Hua Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Epithelial Barrier ◽

Airway Epithelial ◽

Barrier Integrity

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EGCG promotes PRKCA expression to alleviate LPS-induced acute lung injury and inflammatory response

Scientific Reports ◽

10.1038/s41598-021-90398-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mian Wang ◽

Hua Zhong ◽

Xian Zhang ◽

Xin Huang ◽

Jing Wang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Signaling Pathway ◽

Weight Ratio ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Protective Mechanism ◽

High Morbidity ◽

Inflammatory Factor ◽

Egcg Treatment

AbstractAcute lung injury (ALI), which could be induced by multiple factors such as lipopolysaccharide (LPS), refer to clinical symptoms of acute respiratory failure, commonly with high morbidity and mortality. Reportedly, active ingredients from green tea have anti-inflammatory and anticancer properties, including epigallocatechin-3-gallate (EGCG). In the present study, protein kinase C alpha (PRKCA) is involved in EGCG protection against LPS-induced inflammation and ALI. EGCG treatment attenuated LPS-stimulated ALI in mice as manifested as improved lung injury scores, decreased total cell amounts, neutrophil amounts and macrophage amounts, inhibited the activity of MPO, decreased wet-to-dry weight ratio of lung tissues, and inhibited release of inflammatory cytokines TNF-α, IL-1β, and IL-6. PRKCA mRNA and protein expression showed to be dramatically decreased by LPS treatment while reversed by EGCG treatment. Within LPS-stimulated ALI mice, PRKCA silencing further aggravated, while PRKCA overexpression attenuated LPS-stimulated inflammation and ALI through MAPK signaling pathway. PRKCA silencing attenuated EGCG protection. Within LPS-induced RAW 264.7 macrophages, EGCG could induce PRKCA expression. Single EGCG treatment or Lv-PRKCA infection attenuated LPS-induced increases in inflammatory factors; PRKCA silencing could reverse the suppressive effects of EGCG upon LPS-stimulated inflammatory factor release. In conclusion, EGCG pretreatment inhibits LPS-induced ALI in mice. The protective mechanism might be associated with the inhibitory effects of PRKCA on proinflammatory cytokine release via macrophages and MAPK signaling pathway.

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