MicroRNA modulate alveolar epithelial response to cyclic stretch.

Background: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression implicated in multiple cellular processes. Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator-induced lung injury. We propose that miRNAs may regulate some of the stretch response, and therefore hypothesized that miRNAs would be differentially expressed between cyclically stretched and unstretched rat alveolar epithelial cells (RAECs).

Role of Nrf2 in retinal vascular development and the vaso-obliterative phase of oxygen-induced retinopathy.

In the initial stage of retinopathy of prematurity (ROP), hyperoxia causes retinal blood vessel obliteration. This is thought to occur in part through oxidative stress-induced apoptosis of endothelial cells. This study was designed to determine what role NF-E2-related factor 2 (Nrf2) plays in this process.

Cyclic stretch magnitude and duration affect rat alveolar epithelial gene expression.

Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses; but the mechanisms that regulate ventilator-associated lung injury and inflammation remain unclear. Analysis of the genomic response of the lung has been performed in intact lungs ventilated at large tidal volumes. This study is the first to study the genomic response of cultured primary alveolar epithelial cells undergoing large and moderate physiologic cyclic stretch.

Epidermal growth factor receptor (EGFR) regulates mechanical ventilation-induced lung injury in mice.

Mechanical ventilation (MV) is used as therapy to support critically ill patients; however, the mechanisms by which MV induces lung injury and inflammation remain unclear. Epidermal growth factor receptor (EGFR)-mediated signaling plays a key role in various physiologic and pathologic processes, which include those modulated by mechanical and shear forces, in various cell types. We hypothesized that EGFR-activated signaling plays a key role in ventilator-induced lung injury and inflammation (VILI).

Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice.

Rationale: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear.

Objectives: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor that regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI) and that antioxidant supplementation attenuates this effect.