Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner

Abstract Fine particulate matter is a well‐known air pollutant threatening public health. Studies have confirmed long‐term exposure to the particles could decrease the pulmonary function, induce asthma exacerbation, and chronic obstructive pulmonary disease, as well as increase the incidence and mortality of lung cancer. A clinical study has explored that the prevalence and risks of vitamin D (VD) deficiency in various chronic disease and toxins induced tissue damage. Our current study aimed to explore the mechanism and further therapeutic potential of VD administration to ameliorate fine particles exposure induced pulmonary damage in vivo and in vitro. To elucidate the effects and mechanisms of VD in particles‐induced pulmonary damage, a murine model was established with fine particles intratracheal instillation along with VD intramuscular injection. Our study demonstrated that treatment with VD attenuated particles‐induced pulmonary damage and promoted tissue repair by repressing of TGFβ1 signaling pathway and upregulation of MMP9 expression. VD treatment could also regulate the autophagy‐related signals along with activation of Nrf2 transcription factor. Furthermore, the results from the in vitro study demonstrated that VD protected against particles‐induced cells' damage through the induction of autophagy in an Nrf2‐dependent manner. VD treatment caused the degradation of P62 and its bound Keap1, which decreased the Nrf2 ubiquitination and increasing its protein stability. Our work explored a novel potential mechanism in the protection of VD in particles‐induced pulmonary injury and tissue repair, and could further bring insights into exploring antifine particles exposure caused inflammation among other natural products and contributes to inflammation disease medical therapies.