Conclusion
Our study revealed pivotal transcriptional shifts in ATII cells after LPS exposure, particularly in nine key lipid and cholesterol metabolism genes. This altered expression might disrupt the lipid balance, ultimately affecting PS function. This finding deepens our understanding of the aetiology of ARDS and may lead to new therapeutic directions.
Methods
ATII cells were identified using immunofluorescence targeting surface-active protein C. We used 24-h lipopolysaccharide (LPS)-induced ATII cells as an ARDS cell model. The efficacy of the injury model was gauged by detecting the presence of tumour necrosis factor-α and interleukin-6. RNA-seq analysis was performed to investigate the dynamics of PS deviation in unaltered and LPS-exposed ATII cells.
Objective
Alveolar type II (ATII) cells produce pulmonary surfactant (PS) essential for maintaining lung function. The aberration or depletion of PS can cause alveolar collapse, a hallmark of acute respiratory distress syndrome (ARDS). However, the intricacies underlying these changes remain unclear. This study aimed to elucidate the mechanisms underlying PS perturbations in ATII cells using transcriptional RNA-seq, offering insights into the pathogenesis of ARDS.
Results
Whole-transcriptome sequencing revealed that LPS-stimulated ATII cells showed significantly increased transcription of genes, including Lss, Nsdhl, Hmgcs1, Mvd, Cyp51, Idi1, Acss2, Insig1, and Hsd17b7, which play key roles in regulating cholesterol biosynthesis. We further verified gene levels using real-time quantitative PCR, and the results showed that the mRNA expression of these genes increased, which was consistent with the RNA-seq results.