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 D3 in chronic particle-exposure-associated lung fibrosis and tissue remodeling was investigated. In vivo studies showed that vitamin D3 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 in vitro systems of co-culture of macrophages with lung epithelium or fibroblast were built. The results confirmed that vitamin D3 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 D3 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.