Dataset Information

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome.

ABSTRACT:

Background

Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear.

Methods

We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. Differentially expressed genes (DEGs) in AT2 were identified by the criteria |log2FC| ≥ 0.25 and P < 0.05 with DESeq2. A protein interaction network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software to identify hub genes. We then constructed an ARDSp rat model through induction by lipopolysaccharide (LPS) airway instillation. Left lung RNA was extracted and sequenced via Illumina Hiseq platforms. Analysis of the rat RNA sequencing data was then used to verify hub genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the identified hub genes.

Results

In AT2, a total of 289 genes were identified as differentially expressed between those from ARDSp patients and healthy donors, and these included 190 upregulated and 99 downregulated genes. Ten hub genes were further identified (RPS27A, ACTG1, CAV1, HSP90AA1, HSPA5, CCND1, ITGA3, B2M, NEDD4L, and SEMA5A). There was a similar expression trend of HSPA5 between rat RNA and snRNA sequencing data.

Discussion

ARDSp altered the gene expression profile of AT2. The identified hub genes were enriched in biological processes mainly involved in cell growth and transformation. Relatedly, ferroptosis and autophagy are possibly involved in AT2 injury during ARDSp. These novel insights into ARDSp may aid the discovery of potential targets for the diagnosis and treatment of ARDSp.

SUBMITTER: Chen H

PROVIDER: S-EPMC10300320 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome.

Chen Haoran H Ding Jinqiu J Xue Haoyue H Tang Xinyi X Yan Yao Y Xie Yongpeng Y

Heliyon 20230612 6

<h4>Background</h4>Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear.<h4>Methods</h4>We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. D ...[more]

PMID: 37389073

Similar Datasets

Project description:BackgroundAltered coagulation and alveolar injury are the hallmarks of acute respiratory distress syndrome (ARDS). However, whether the biomarkers that reflect pathophysiology differ depending on the etiology of ARDS has not been examined. This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as "ARDS without common risk factors" based on the Berlin definition.MethodsThis retrospective, observational study included adult patients who were admitted to the intensive care unit (ICU) at a university hospital with a diagnosis of ARDS with no indirect risk factors. Plasma biomarkers (thrombin-antithrombin complex [TAT], plasminogen activator inhibitor [PAI]-1, protein C [PC] activity, procalcitonin [PCT], surfactant protein [SP]-D, and KL-6) were routinely measured during the first 5 days of the patient's ICU stay.ResultsAmong 138 eligible patients with ARDS, 51 were excluded based on the exclusion criteria (n = 41) or other causes of ARDS (n = 10). Of the remaining 87 patients, 56 were identified as having dARDS and 31 as having iARDS. Among the iARDS patients, TAT (marker of thrombin generation) and PAI-1 (marker of inhibited fibrinolysis) were increased, and PC activity was above normal. In contrast, PC activity was significantly decreased, and TAT or PAI-1 was present at much higher levels in dARDS compared with iARDS patients. Significant differences were also observed in PCT, SP-D, and KL-6 between patients with dARDS and iARDS. The receiver operating characteristic (ROC) analysis showed that areas under the ROC curve for PC activity, PAI-1, PCT, SP-D, and KL-6 were similarly high for distinguishing between dARDS and iARDS (PC 0.86, P = 0.33; PAI-1 0.89, P = 0.95; PCT 0.89, P = 0.66; and SP-D 0.88, P = 0.16 vs. KL-6 0.90, respectively).ConclusionsCoagulopathy and alveolar epithelial injury were observed in both patients with dARDS and with iARDS. However, their biomarker profiles were significantly different between the two groups. The different patterns of PAI-1, PC activity, SP-D, and KL-6 may help in differentiating between these ARDS subtypes.

Dataset Information

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome.

Background

Methods

Results

Discussion

Publications

SnRNA-Seq analysis reveals ten hub genes associated with alveolar epithelial cell injury during pulmonary acute respiratory distress syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets