PM 2.5 promotes pulmonary fibrosis by mitochondrial dysfunction

Abstract Pulmonary fibrosis is known as an incurable lung disorder with irreversible progression of chronic injury, myofibroblast proliferation, extracellular matrix (ECM) accumulation, and tissue scarring. Atmospheric particulate matter 2.5 (PM 2.5 ) is implicated as a risk factor of several diseases, especially lung diseases such as pulmonary fibrosis. The molecular mechanism which participates PM 2.5 ‐induced pulmonary fibrosis in type II alveolar cells (AEII) has yet to be determined. Our results proved that short‐ and long‐term exposure to PM 2.5 significantly stimulated epithelial‐mesenchymal transition (EMT) activity in AEII cells, according to, changes in gene signature analyzed by RNA‐seq and cell morphology. Furthermore, Gene Ontology (GO) enrichment analysis also suggested that mitochondrial dysfunction was related to progression of pulmonary fibrosis in AEII after PM 2.5 exposure. We observed a marked decline in mitochondria membrane potential (MMP), as well as fragmented mitochondria, in AEII cells exposed to PM 2.5 , which suggests that energy metabolism is suppressed after PM 2.5 exposure. We also confirmed that PM 2.5 exposure could influence the expression levels of Mfn1, Mfn2, and Drp1 in AEII. Pretreatment of mitochondrial fusion promoter M1 was able to reverse mitochondrial dysfunction as well as EMT in AEII. These data suggested the key role of mitochondrial fragmentation in AEII, which was induced by PM 2.5 exposure, and participated pathogenesis of pulmonary fibrosis. Finally, we investigated the response of lung tissue exposed to PM 2.5 in vivo. The data indicated that the lung tissue exposed to PM 2.5 obviously induced collagen accumulation. Moreover, IHC results revealed that PM 2.5 enhanced Drp1 expression but suppressed Mfn1 and Mfn2 expression in lung tissue. The current study provides novel insight of pulmonary fibrosis caused by PM 2.5 exposure.