Particulate Matter Increases Bone Morphogenetic Protein 2 in Lung Fibroblasts

Particulate matter less than 2.5 μm (PM 2.5 ) contributes to many chronic respiratory disorders, but the mechanisms for this are not fully understood. The actions of PM 2.5 on lung epithelial cells have been well studied, but their effect on lung fibroblasts has not been as extensively reported. Bone morphogenetic protein (BMP) 2, part of the transforming growth factor cytokine family, plays crucial roles in development, morphogenesis, and repair, and functions as a critical mediator in the pathogenesis of lung diseases such as pulmonary fibrosis and chronic obstructive lung disease. Here, we investigate the impact of PM 2.5 on fibroblast BMP2 production and the role of BMP2 in mediating fibroblast-to-myofibroblast differentiation and matrix generation. Treatment of fibroblasts to PM 2.5 resulted in a dose-dependent rise in BMP2 mRNA and protein secretion, which was specific to BMP2 and not observed with other BMP family members. In normal quiescent fibroblasts, BMP2 induced an increase in collagen and α-smooth muscle actin expression. Interestingly, BMP2 exerted an opposite effect in TGF-β1-differentiated myofibroblasts, whereby BMP2 downregulated collagen levels. These differential responses aligned with variations in p38 and ERK1/2 phosphorylation. Fibroblasts treated with high concentrations of PM 2.5 demonstrated reduced collagen and α-smooth muscle actin expression, an effect reversed by BMP2 silencing or gremlin, a BMP2 antagonist. Overall, PM 2.5 was observed to induce BMP2 production in fibroblasts and this was associated with suppression of fibroblast activation and matrix production by PM 2.5 . These findings highlight a potential mechanism whereby PM 2.5 contributes to lung disease via impairment of fibroblast regenerative and repair capabilities.