Hyperoxia-induced oxidative stress enhances TMEM106B to impair ULK1-mediated autophagy via TLR3/JNK signaling.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and is a major health hazard for preterm infants worldwide. Hyperoxia-induced oxidative stress is one of the major risk factors for the development of BPD, and ideas for timely intervention in the development of BPD are urgently needed to understand this mechanism. The transmembrane protein TMEM106B is a key molecule in the regulation of autophagy function. However, its biological function in BPD remains elusive. In this study, we evaluated that TMEM106B expression was significantly elevated in BPD patients compared with healthy patients with an area under the receiver-operating characteristic curve of 0.7122, suggesting that TMEM106B expression may be associated with the development of BPD. We further found that TMEM106B expression levels were significantly elevated in the neonatal rat BPD model compared with healthy control rats. Hyperoxic stimulation promoted macrophage TMEM106B expression. Consistent with these findings, macrophage reactive oxygen species and apoptosis levels were decreased and autophagy was enhanced after TMEM106B silencing. Hyperoxic stimulation resulted in a significant decrease in TMEM106B expression after TLR3-JNK inhibition. Taken together, our results suggest that hyperoxia-induced oxidative stress inhibited macrophage autophagy by enhancing TMEM106B through the TLR3/JNK signaling pathway and elucidated its TMEM106B-ULK1-dependent mechanism. Therefore, our data support further investigation of TMEM106B as a key molecule interfering with BPD development.