FAM134B Attenuates Apoptosis and EMT by Inhibiting M1 Macrophage Polarization Via PI3K/AKT Pathway in Rat Lungs Exposed to Hyperoxia

Abstract

Oxygen therapy is widely used in pulmonary disease and critical care resuscitation. Unfortunately, prolonged exposure to high concentrations of oxygen may cause oxygen toxicity, leading to hyperoxia-induced acute lung injury (HALI). The injurious effects of lung following hyperoxia exposure are well established, and the effects include cell apoptosis and epithelial-to-mesenchymal transition (EMT). HALI responds to the inflammatory response induced by M1 macrophage polarization. Suppressing inflammation in macrophages protects against HALI. The PI3K/AKT pathway promotes cell survival in oxidative stress injury. Activation of Akt is a beneficial response protects against hyperoxic stress. FAM134B activates ER-phagy through binding to LC3B, ER fragments are degraded by ER-phagy, and ER homeostasis is maintained. We hypothesized that FAM134B may regulate macrophage polarization and inflammatory responses in hyperoxia-exposed rats via PI3K/AKT signaling pathway, thereby attenuating HALI.

In this study, we clarified the role of FAM134B in lung tissues of hyperoxia-exposed rats and the effect of FAM134B on macrophage polarization. The expression of FAM134B and PI3K/AKT pathway were inhibited in rat lung tissues after hyperoxia exposure. We found that overexpression of FAM134B activated the PI3K/AKT pathway and reduced apoptosis and EMT in rat lung tissues after hyperoxia exposure. The PI3K/AKT pathway inhibitor, LY294002, reversed the protective effect of FAM134B in hyperoxia-exposed rats. Overexpression of FAM134B reduced the release of inflammatory factors (IL-1β, TNF-ɑ, IL-6) and polarization of M1 macrophages after hyperoxia exposure, and LY294002 reversed this effect.

In conclusion, our study showed that FAM134B inhibits M1 macrophage polarization and inflammatory factor release via PI3K/AKT pathway and attenuates apoptosis and EMT in rat lung of hyperoxia-exposed FAM134B is a key target for HALI, which provides new ideas for the treatment of HALI.