Asthma is a common chronic airway inflammatory disease characterized by chronic airway inflammation, resulting in mucus overproduction, airway hyperresponsiveness and the remodeling of the walls. Physiologically, airway epithelial cells acts as the first-line barrier to prevent against foreign stimulus and maintain airway homeostasis (Hellings and Steelant, 2020). Meanwhile, airway epithelial cells exposed to allergens directly drive oxidative stress in terms of reactive oxygen (ROS) and nitrogen (RNS) species generation, which leads to apoptosis and injury of airway epithelium implicated in asthma pathogenesis (Lambrecht and Hammad, 2013, Sauler et al., 2019, James et al., 2021).

Increasing evidence has revealed that excessive ROS production is greatly correlated with mitochondrial dysfunction under allergic conditions (Prakash et al., 2017, Zuo and Wijegunawardana, 2021). In this regard, damaged mitochondria are further recognized and selectively degraded by autophagy, also termed as mitophagy. Mitophagy is an evolutionarily conversed self-degradation process by which superfluous or impaired organelles are removed to stabilize mitochondria function. In particular, oxidative stress-evoked mitophagy helps to reduce the accumulation of dysfunctional mitochondria and in turn prevents ROS generation, thereby repressing cellular homeostasis disturbance and mitochondria-induced inflammation (Sachdeva et al., 2019). Therefore, a promotion of mitophagy and elimination of ROS-induced mitochondria impairment may provide novel insight into therapies for asthma-associated airway injury under environmental exposures.

Apelin, also known as APLN, is the endogenous ligand of a formerly orphan G protein coupled receptor APJ. Apelin contains a variety of bioactive isoforms including Apelin-12, Apelin-13, Apelin-17, and Apelin-36. Notably, Apelin-13 exhibits the highest activity amongst the apelin isoforms (Yan et al., 2020). Accumulating studies verified the cytoprotective and anti-oxidative properties of Apelin-13 in many diseases such as neuroinflammation, ischemia-reperfusion injury, myocardial damage, etc (Luo et al., 2019, Shao et al., 2021, Garcia-Juarez et al., 2022). Nevertheless, the impact of Apelin-13 on airway epithelial injury in the setting of asthma is still unknown, and how Apelin-13 modulates mitophagy under oxidative stress has not been elucidated yet.

Therefore, we intended to further explore whether Apelin-13 was implicated in the regulation of mitophagy in oxidative stress-associated airway epithelial injury and investigate the potential molecular mechanism.