2. Academic Validation
  3. Mitochondria-derived peptide MOTS-c alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice by activating Nrf2 pathway

Mitochondria-derived peptide MOTS-c alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice by activating Nrf2 pathway

  • Eur J Pharmacol. 2026 Mar 28:1019:178726. doi: 10.1016/j.ejphar.2026.178726.
Dan Chen 1,  Mei-Hui Zhou 1,  Wei-Ying Zhu 2,  Zhi-Xuan Xing 1,  Sheng-Peng Li 1,  Ya-Xian Wu 1,  Xiao-Lin Sun 3,  Ping Sun 4,  Qing-Feng Pang 5
Affiliations

Affiliations

  • 1 Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
  • 2 Department of Obstetric, Maternity and Child Health Care Affiliated Hospital, Jiaxing University, Jiaxing, 314000, China.
  • 3 Linyi Maternal and Child Health Hospital, Qinghe South Road, Luozhuang District, Linyi City, 276000, Shandong Province, China.
  • 4 Department of Pathology, Jiangnan University Medical Center, Wuxi, 214002, Jiangsu Province, China. Electronic address: [email protected].
  • 5 Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, China. Electronic address: [email protected].
PMID: 41802484 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.

Keywords

Angiogenesis; Anti-oxidative; Bronchopulmonary dysplasia; MOTS-c; Nrf2.

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