Role of PI3K/Akt/mTOR pathway-mediated macrophage autophagy in affecting the phenotype transformation of lung fibroblasts induced by silica dust exposure.

Objectives: The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the main signaling pathways related to autophagy. Autophagy plays a key role in the formation of silicosis fibrosis. The phenotypic transformation of lung fibroblasts into myofibroblasts is a hallmark of the transition from the inflammatory phase to the fibrotic phase in silicosis.

MiR-30a inhibits silica dust-induced epithelial-mesenchymal transition by targeting Snail.

The mechanism of action of MicroRNA-30a(miR-30a) and Snail, a transcription factor, in silica(SiO2) dust-induced pulmonary EMT and secondary pulmonary fibrosis remains elusive. In this study, the cellular EMT model induced by the stimulation of A549 cells with SiO2 was established. A549 cells were transfected with miR-30a mimic and miR-30a inhibitor and the SNAIL gene was silenced to examine the mechanism of miR-30a targeting Snail to regulate silica dust-induced EMT.

SiO dust induces inflammation and pulmonary fibrosis in rat lungs through activation of ASMase/ceramide pathway.

The role of ASMase/ceramide signaling pathway in the development of silicosis needs to be verified by in vivo experiments. We investigated the role of the ASMase/ceramide signaling pathway in the progression of silicosis and the effect of desipramine (DMI) (1 mg/mL) on the development of silicosis, by establishing a silica (1 mL, 50 mg/mL) dust-contaminated rat silicosis model and administering the ASMase inhibitor, DMI, to the dust-contaminated rats. The results showed that the levels of interleukin (IL)-1β and IL-6 were increased in the lung tissues of the rats in the dust-contaminated group at the initial stage after dusting; the inflammatory cell aggregation in the lung tissue was increased.