Dan Chen, Mei-hui Zhou, Wei-ying Zhu, Zhi-xuan Xing, Sheng-peng Li, Ya-xian Wu, Xiao-lin Sun, Ping Sun, Qing-feng Pang
Wuxi School of Medicine, Jiangnan University Medical Center and Jiangnan University. Maternity and Child Health Care Affiliated Hospital, Jiaxing University. Linyi Maternal and Child Health Hospital.
China
European Journal of Pharmacology
Eur J Pharmacol 2026;
DOI: 10.1016/j.ejphar.2026.178726
Abstract
Oxidative stress play key roles in the pathogenesis of bronchopulmonary dysplasia (BPD). MOTS-c is a mitochondria-derived peptide containing 16 amino acids that is reported to be involved in the treatment of oxidative stress-related diseases. However, whether MOTS-c functions on hyperoxia-induced BPD remains unknown. The purpose of this study was to investigate the potential therapeutic effect and mechanism of MOTS-c on hyperoxia-induced BPD. Here, hyperoxia (70% O2) was used to mimic the murine BPD model. We found that MOTS-c content was reduced in hyperoxia-induced BPD mice. Exogenous MOTS-c supplementation alleviated growth retardation, attenuated alveolar simplification, and pulmonary vascular abnormalities in hyperoxia-induced BPD mice. Besides, MOTS-c supplement increased cell viability, inhibited cell death and promoted tube formation in hyperoxia-stimulated HUVECs. Moreover, MOTS-c administration significantly inhibited inflammation and oxidative stress both in vivo and in vitro. In addition, the beneficial effect of MOTS-c was Nrf2 dependent, since the anti-inflammation, anti-oxidative and pro-angiogenic effects of MOTS-c were offset in ML385 (a specific Nrf2 inhibitor) treated HUVECs or in Nrf2 deficiency mice. In conclusion, MOTS-c protects against hyperoxia-induced lung alveolar simplification and abnormal angiogenesis in an Nrf2-dependent manner. MOTS-c emerges as a potential anti-oxidant therapeutic agent to treat hyperoxia-induced BPD.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
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