Melatonin prevents lung injury by regulating apelin 13 to improve mitochondrial dysfunction

Pulmonary fibrosis is a progressive disease characterized by epithelial cell damage, fibroblast proliferation, excessive extracellular matrix (ECM) deposition, and lung tissue scarring. Melatonin, a hormone produced by the pineal gland, plays an important role in multiple physiological and pathological responses in organisms. However, the function of melatonin in the development of bleomycin-induced pulmonary injury is poorly understood. In the present study, we found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depends on type II alveolar epithelial cells (AECIIs) and is linked to mitochondrial integrity. We also found that melatonin reduced the production of reactive oxygen species (ROS) and prevented apoptosis and senescence in AECIIs. Luzindole, a nonselective melatonin receptor antagonist, blocked the protective action of melatonin. Interestingly, we found that the expression of apelin 13 was significantly downregulated in vitro and in vivo and that this downregulation was reversed by melatonin. Furthermore, ML221, an apelin inhibitor, disrupted the beneficial effects of melatonin on alveolar epithelial cells. Taken together, these results suggest that melatonin alleviates lung injury through regulating apelin 13 to improve mitochondrial dysfunction in the process of bleomycin-induced pulmonary injury. Lung disease: managing misbehaving mitochondria The hormone melatonin could protect lung cells from the damage associated with respiratory diseases such as pulmonary fibrosis. Several studies have linked such damage with abnormal activity of the mitochondria, with these essential metabolic organelles churning out damaging ‘reactive oxygen species’ (ROS), compounds that induce premature cell aging and death. Melatonin can mitigate ROS production, and researchers led by Haihai Liang at China’s Harbin Medical University have demonstrated that it can prevent injury to airway epithelial cells in a mouse model of lung disease. Melatonin treatment countered much of the damage, resulting in significantly longer survival, and the team identified a target molecule in the mitochondria that may be responsible for this effect. This approach could offer hope for a family of diseases with a poor prognosis and limited treatment options.