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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Mitochondria-derived peptide MOTS-c alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice by
Dan Chen1, Mei-Hui Zhou1, Wei-Ying Zhu2
1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, China.
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.
Insights
Mitochondria-derived peptide MOTS-c, reduced in hyperoxia-induced bronchopulmonary dysplasia (BPD), alleviates lung injury. Its protective effects against oxidative stress and inflammation in BPD are dependent on the Nrf2 pathway.
Area of Science:
- Biomedical research
- Molecular biology
- Pulmonary medicine
Background:
- Oxidative stress is a key factor in bronchopulmonary dysplasia (BPD) pathogenesis.
- MOTS-c, a mitochondria-derived peptide, shows promise in treating oxidative stress-related diseases.
- The role of MOTS-c in hyperoxia-induced BPD is currently unknown.
Purpose of the Study:
- To investigate the therapeutic potential and underlying mechanisms of MOTS-c in a murine model of hyperoxia-induced BPD.
- To determine if MOTS-c supplementation can mitigate BPD-related lung damage.
- To elucidate the molecular pathways involved in MOTS-c's protective effects.
Main Methods:
- A murine model of hyperoxia-induced BPD was established using 70% O2.
- MOTS-c levels were measured in hyperoxia-exposed mice.
- Exogenous MOTS-c was administered to assess its effects on BPD symptoms, lung histology, and pulmonary vascularization.
- In vitro studies using hyperoxia-stimulated human umbilical vein endothelial cells (HUVECs) evaluated cell viability, death, and tube formation.
- The role of the Nrf2 pathway was assessed using an Nrf2 inhibitor (ML385) and Nrf2-deficient mice.
Main Results:
- MOTS-c levels were decreased in hyperoxia-induced BPD mice.
- MOTS-c supplementation improved growth, reduced alveolar simplification, and corrected pulmonary vascular abnormalities in BPD mice.
- In vitro, MOTS-c enhanced HUVEC viability, reduced cell death, and promoted tube formation.
- MOTS-c significantly inhibited inflammation and oxidative stress both in vivo and in vitro.
- The protective effects of MOTS-c were dependent on Nrf2 activation, as they were abolished by Nrf2 inhibition or deficiency.
Conclusions:
- MOTS-c demonstrates significant protective effects against hyperoxia-induced lung injury in a murine BPD model.
- The therapeutic benefits of MOTS-c, including anti-inflammatory, anti-oxidative, and pro-angiogenic actions, are mediated through the Nrf2 pathway.
- MOTS-c represents a promising therapeutic candidate for treating hyperoxia-induced BPD due to its antioxidant properties.
