Particulate matter increases bone morphogenetic protein 2 in lung fibroblasts

Particulate matter (PM) < 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 2 (BMP2), part of the transforming growth factor cytokine family, plays crucial roles in the development, morphogenesis, 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 through impairment of fibroblast regenerative and repair capabilities.NEW & NOTEWORTHY Particulate matter <2.5 µm (PM_2.5) from air pollution contributes to many different lung diseases, but the mechanisms are not fully understood. Here, we demonstrated that PM_2.5 caused an upregulation of bone morphogenetic protein 2 (BMP2) in lung fibroblasts. BMP2 can promote myofibroblast differentiation or inhibit collagen expression, depending on the context, and can be a means by which PM_2.5 contributes to fibrotic and nonfibrotic lung diseases.