Lung microvascular endothelial inflammation and barrier dysfunction play critical roles in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Despite recent scientific advances, the mortality of ALI/ARDS is still extremely high because the molecular mechanisms involved in ALI/ARDS remain unclear. In a recent issue of the journal Advanced Science, Baoyinna and colleagues reported that deubiquitinase USP30 induces lung microvascular inflammation and endothelial barrier disruption through the S-adenosylmethionine (SAM) cycle, DNA methylation, and miR-30a-5p down-regulation in ALI/ARDS. Their findings provide a strong rationale for targeting microRNAs, S-adenosylmethionine, DNA methylation, and deubiquitinating enzymes as potential therapeutic strategies for the treatment of ALI/ARDS.
Precise labeling of alveolar type 2 (AT2) cells is essential for elucidating lung development and injury responses. In this study, we evaluated Abca3 and Etv5-based genetic strategies for labeling AT2 cells in murine models. Using targeted genetic approaches, we generated Abca3-rtTA and Etv5-rtTA knock-in mouse lines and crossed them with pTRE-H2BGFP to create inducible reporter models driven by Abca3 or Etv5. Labeling specificity and efficiency were assessed by flow cytometry and co-immunostaining. Our results show that both Abca3 and Etv5 strategies faithfully label AT2 cells across developmental stages and following lung injury. Comprehensive analyses confirmed the high specificity and efficiency of labeling. These Abca3- and Etv5-driven systems offer robust tools for investigating AT2 cell biology and pathology and may serve as effective drivers for tetO-mediated gene knockout or overexpression studies specifically in AT2 cells in mouse models.
