Multi-omics Analysis Reveals the Effects of LPS-induced Acute Lung Injury in Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216943 | GEO | 2023/11/11
REPOSITORIES: GEO
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Project description:This project investigates the dynamic lung proteome in a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). C57BL/6N mice were exposed to LPS via intratracheal nebulization to induce ALI, and lung tissues were collected at multiple time points (non-stimulated controls, and days 1, 3, 7 and 14 after LPS challenge) to capture the onset, peak and resolution phases of lung injury.
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Project description:Rationale: Geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, regulates various pathological processes through balancing the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. We sought to investigate whether GGPPS1 plays a role in mediating acute lung injury (ALI) using a mouse model of inflammation. Methods: Lipopolysaccharide (LPS) was intra-tracheally instilled to induce ALI in lung specific GGPPS1 knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells (AECs) was examined at different time points. Alveolar exudate, neutrophil infiltration, lung injury and cell death were determined. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro. Results: GGPPS1 levels increased significantly in lung tissues from LPS-induced ALI mice, where it showed a time- and dose-dependent increase in alveolar epithelial cells. Specific deletion of pulmonary GGPPS1 reduced the alveolar exudate and attenuated the severity of lung injury through inhibiting apoptosis of AECs. However, GGPPS1 deletion had limited effect on neutrophil counts and TNF-α levels in alveolar fluids. Deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1β release and pyroptosis, by down-regulating NLRP3 expression. Conclusions: Inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI, predominantly by suppressing NLRP3 inflammasome activation.
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Project description:This dataset presents transcriptomic profiles of lung tissue from a murine model of LPS-induced acute lung injury (ALI) following treatment with Renshen Baidu Powder (RSBD). LPS induced a robust inflammatory gene signature, which was significantly reversed by RSBD.
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Project description:Purpose: Acute lung injury (ALI) is a severe clinical disorder characterized by diffused capillary-alveolar barrier damage and noncardiogenic lung edema induced by excessive inflammation reactions. Nogo-B, a member of the reticulon 4 protein family, plays a critical role in modulating macrophages and neutrophils’ function in inflammation. Its role in ALI remains unclear. Methods: Pulmonary expression of Nogo-B was investigated in a LPS-induced ALI mice model. The effects and the underline mechanisms of Nogo-B expression on the severity of lung injury was assessed using histological examination, Bronchoalveolar lavage fluid (BALF) protein and inflammatory cells and cytokines measurement, and microarray analysis. Results: Nogo-B was normally highly expressed in the lungs of naïve C57BL/6 mice. Intra-tracheal instillation of LPS significantly repressed the Nogo-B expression in lung tissues and BALF cells of ALI mice. In addition, over-expression of pulmonary Nogo-B using an adenovirus vector which expresses a Nogo-B-RFP-3-flag fusion protein (Ad-Nogo-B) significantly prolonged the survival time of mice challenged with lethal dose of LPS. Histological results and BALF protein measurement convinced that Ad-Nogo-B treated mice had less severity of lung injury and alveolar protein exudation, as compared with control adenovirus treated mice (Ad-RFP). They also had higher MCP-1 secretion and alveolar macrophages infiltration, but lower neutrophils infiltration. Finally, using microarray analysis, we identified a protective gene, PTX3, was highly elevated in Ad-Nogo-B treated mice. Conclusions: Nogo-B played a protective role in LPS-induced ALI, which might exert its role through modulation of inflammatory response and PTX3 secretion. A total of 12 samples from mice treated with or without LPS in the presence of Ad-Nogo-B or Ad-RFP transfection (n=3 for each group)
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Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways and the function of all RNAs in a certain functional state of a specific cell was studied, mainly including non-coding RNAs.The aim of this study was to compare lung tissue transcriptome analysis (RNA-SEQ) with microarray and quantitative reverse transcription polymerase chain reaction (QRT-PCR) methods for LPS-induced acute lung injury and to evaluate the optimal high-throughput data analysis protocol. Methods: LncRNA profiles of normal lung tissue and LPS-induced acute lung injury after 24h in mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 4000 Results: A total of 8,610 lncRNAs were identified in the normal and LPS groups. Conclusions: Our study represents detailed analysis of lung tissue transcriptomes, withh biological replicates, generated by RNA-seq technology. Novel ideas are presented to expand our knowledge on the regulation mechanisms of lncRNA-related ceRNAs in the pathogenesis of ALI.
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Project description:Multi-omics Analysis Reveals the Effects of LPS-induced Acute Lung Injury in Mice
| PRJNA896217 | ENA
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