TGF-β1 mediated MAPK signaling pathway promotes collagen formation induced by Nano NiO in A549 cells.

Nickel oxide nanoparticles (Nano NiO) could induce pulmonary fibrosis, however, the mechanisms are still unknown. The aim of the present study was to explore the roles of transforming growth factor-β1 (TGF-β1), mitogen-activated protein kinase (MAPK) pathway and MMPs/TIMPs balance in Nano NiO-induced pulmonary fibrosis. For that purpose, we first established Nano NiO-induced human lung adenocarcinoma epithelial cells (A549 cells) model of collagen excessive formation through detecting the levels of hydroxyproline (Hyp) and type I collagen (Col-I). Then the protein levels of TGF-β1, MAPKs, and MMPs/TIMPs were assessed by Western blot. The results showed that Nano NiO resulted in the increased contents of Hyp, Col-I, and TGF-β1, the MAPK pathway activation and MMPs/TIMPs imbalance with a dose-dependent manner. In addition, to investigate whether TGF-β1 mediated MAPK signaling pathway, A549 cells were treated by 100 μg/mL Nano NiO combined with TGF-β1, p38 MAPK, and ERK1/2 inhibitors (10 μM SB431542, 10 μM SB203580, and 10 μM U0126), respectively. We found that MAPK signal pathway was suppressed by TGF-β1 inhibitor. Meanwhile, the increased contents of Hyp and Col-I, and MMPs/TIMPs imbalance were alleviated by the p38 MAPK and ERK1/2 inhibitors, respectively. These findings indicated that the MAPK pathway and MMPs/TIMPs imbalance were involved in collagen excessive formation induced by Nano NiO.