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.