TRIM72 mediates lung epithelial cell death upon hyperoxia exposure.

Abstract

Premature infants often require oxygen (O2) therapy for respiratory distress syndrome; however, excessive use of O2 can cause clinical conditions such as bronchopulmonary dysplasia. Although many treatment methods are currently available, they are not effective in preventing bronchopulmonary dysplasia. Herein, we explored the role of tripartite motif protein 72 (TRIM72), a factor involved in repairing alveolar epithelial wounds, in regulating alveolar cells upon hyperoxia exposure. In this in vivo study, we used Sprague-Dawley rat pups that were reared in room air or 85% O2 for 2 weeks after birth. The lungs were excised for histological analyses, and TRIM72 expression was assessed on postnatal days 7 and 14. For in vitro experiments, RLE-6TN cells (i.e., rat alveolar type II epithelial cells) and A549 cells (i.e., human lung carcinoma epithelial cells) were exposed to 85% O2 for 5 days. The cells were then analyzed for cell viability, and TRIM72 expression was determined. Exposure to hyperoxia reduced body and lung weight, increased mean linear intercept values, and upregulated TRIM72 expression. In vitro study results revealed increased or decreased lung cell viability upon hyperoxia exposure depending on the suppression or overexpression of TRIM72, respectively. Hyperoxia upregulates TRIM72 expression in neonatal rat lung tissue; moreover, it initiates TRIM72-dependent alveolar epithelial cell death, leading to hyperoxia-induced lung injury.