Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation

Abstract

Background: Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. Methods: Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. results: In fully treated animals (LPS + MV + 60% O 2 ) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/ wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. conclusion: MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.

Urine Proteomics for Noninvasive Monitoring of Biomarkers in Bronchopulmonary Dysplasia

“…Additionally, we see major dysregulation of proteins associated with immune effector processes including complement pathway proteins, which is consistent with a previous animal study that identified increased expression of complement components in a newborn rat lung injury model [26]. Of interest, blood coagulation and fibrin clot formation pathways were associated with proteins with statistically significant changes in abundance in our urine proteomics study.…”

Immune System Regulation Affected by a Murine Experimental Model of Bronchopulmonary Dysplasia: Genomic and Epigenetic Findings

“…However, in a study in lung tissue from mechanically ventilated newborn rats with 60% oxygen treatment and LPS-injections, the authors found differentially regulated genes from the immune system, inflammatory response and hematopoiesis, similar to our findings, but after only 6 hours of treatment with oxygen 27 .…”

Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia

“…Similar studies have been undertaken during lung development in rhesus macaques, to highlight cross talk of dynamic functional modules (groups of genes in regulatory networks) during primate lung development (586). Pathological changes to transcriptome were assessed in lungs from rat pups that received intraperitoneal E. coli 026:B6 followed by a period of mechanical ventilation (130). A microarray analysis of the lung transcriptome revealed alternations to MMP expression and the complement system, identifying MMP and complement-mediated pathways as candidate pathogenic factors in the associated lung pathology.…”