Pharmaceutic application of vitamin D3 on particle-induced fibrotic effects through induction of Nrf2 signals

Fine particulate matter, a major air pollutant across the world, causes a series of pulmonary diseases. Vitamin D is a typical vitamin with emerging roles in inflammation and fibrosis. Different situations and diseases need different doses and modes of vitamin D administration, which challenges the existing vitamin D supplementary rules. Thus, studies of vitamin D applications and their mechanisms in various diseases are important for its future therapeutic applications. In this study, the therapeutic application of vitamin D in chronic particle-exposure-associated lung fibrosis and tissue remodeling was investigated. studies showed that vitamin D significantly attenuated fibrosis effects by decreasing α-smooth muscle actin-regulated extracellular matrix deposition and restoring expressions of E-cadherin and N-cadherin. With the importance of activated macrophage in the regulation of local epithelium and fibroblast in the process of tissue fibrosis, two separate systems of co-culture of macrophages with lung epithelium or fibroblast were built. The results confirmed that vitamin D promoted the proliferation of lung epithelium and depressed the fibrosis effects of fibroblasts as well. In addition, our results indicated that the therapeutic effects of vitamin D were through Nrf2 signals. Our work provides convincing experimental evidence for vitamin D therapeutic application to promote tissue repair and improve particle-associated lung fibrosis.