Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide‑induced acute lung injury

Abstract

Mechanical ventilation (MV) and lipopolysaccharide (lPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (lPS)-induced acute lung injury (ali). Gene expression data of adult c57Bl/6 mice with ali induced by inhaling lPS, MV and lPS + MV were downloaded from the Gene expression omnibus database. differentially expressed genes (deGs) associated with MV, lPS and lPS + MV were screened, followed by functional enrichment analysis, protein-protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription-quantitative Pcr. a total of 63, 538 and 1,635 deGs were associated with MV, lPS and lPS + MV, respectively. MV-associated genes were significantly enriched in the 'purine ribonucleotide metabolic process'. lPS and lPS + MV-associated genes were significantly enriched in 'cellular response to cytokine stimulus' and 'cell chemotaxis'. all three conditions were enriched in 'TnF signaling pathway' and 'il-17 signaling pathway'. expression levels of c-X-c motif chemokine ligand (cXcl)2, cXcl3 and cXcl10 were upregulated in the lPS and lPS + MV groups. adenosine A2b receptor, zinc finger and BTB domain-containing 16 and hydroxycarboxylic acid receptor 2 were identified as deGs in the MV group. compared with the control group, early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV-and lPS-induced ali, and MV may enhance the effects of lPS on gene expression. MV may affect urine ribonucleotide metabolic-related processes, whereas lPS may cause cell chemotaxis and cytokine stimulus responses in ali progression. The inflammatory response was shared by MV and lPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ali.

Machine Learning–Based Discovery of a Gene Expression Signature in Pediatric Acute Respiratory Distress Syndrome

“…Although few genes were shared between the primary airway cell and neutrophil reporter assay analysis, there was overlap in the pathways that emerged. The top regulated gene was early growth response (Egr)-1, an immediate-early response transcription factor with a key role in inflammation, extracellular matrix formation, thrombosis, apoptosis, and fibrosis, that are involved in acute lung injury (44)(45)(46). For example, suppression of Egr-1 following immune complex-induced acute lung inflammation in mice with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduced proinflammatory cytokine expression (47).…”

Knockdown of CXCL3-inhibited apoptosis and inflammation in lipopolysaccharide-treated BEAS-2B and HPAEC through inactivating MAPKs pathway

“…21 Bioinformatic analysis has shown that CXCL3 was a differentially expressed gene in mechanical ventilation and LPS-induced mice with acute lung injury, and might be regarded as a potential target for the treatment of acute lung injury. 18 This is the first evidence demonstrating the contribution of CXCL3 to LPSinduced cytotoxicity and inflammation in BEAS-2B and interpreted the data. Yuhui Wang and Linyan Pan prepared the manuscript for publication and reviewed the draft of the manuscript.…”

“…A previous study has shown that CXCL3 was upregulated in lung tissues of mechanical ventilation and LPSinduced mice. 18 Here, LPS also induced upregulation of CXCL3 in BEAS-2B and HPAE cells. Functional assays showed that knockdown of CXCL3 decreased viability, increased apoptosis, and upregulated TNF-α, IL-1β, and IL-18 in LPStreated BEAS-2B and HPAE cells.…”

“…17 Moreover, CXCL3 was found to be a differentially expressed gene in mechanical ventilation and LPS-induced mice with acute lung injury. 18 However, the role of CXCL3 in sepsis-associated acute lung injury has not been reported yet.…”

Screening of Hub Genes Associated with Pulmonary Arterial Hypertension by Integrated Bioinformatic Analysis

“…The TRRUST database contains 800 human transcription factors (TFs) and 828 mouse TFs, with 8444 human and 6552 mouse TFtarget regulatory relationships, respectively [26]. Then, the TRRUST database was used to predicted the TFs of the hub genes [27]. The TF-hub gene interaction pairs with P values <0.05 were selected to establish the regulatory network.…”