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

Abstract

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.

Nano nickel oxide promotes epithelial‐mesenchymal transition through transforming growth factor β1/smads signaling pathway in A549 cells

“…TGF‐β1 plays crucial roles in the nano materials‐induced lung injury including inflammatory response, collagen deposition, and pulmonary fibrosis 17,25 . Our previous study shown that the increasing TGF‐β1 concentration was observed in rats and A549 cells exposed to nano NiO 4,19 . Current results found TGF‐β1 was activated by nano NiO in A549 cells, furtherly verified the role of TGF‐β1.…”

“…17,25 Our previous study shown that the increasing TGF-β1 concentration was observed in rats and A549 cells exposed to nano NiO. 4,19 Current results found TGF-β1 was activated by nano NiO in A549 cells, furtherly verified the role of TGF-β1. Smad3 is a key substrate of TGF-βR1 kinase and mediates signal transduction in the cell biology.…”

“…Nano NiO particles was prepared with the sterilized at 120°C for 30 minutes. The methods of preparation the nano NiO is the same as our previous research 19 …”

JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblasts Transdifferentiation in Graves' Orbital Fibroblasts

“…Additionally, the contribution of p38 and JNK pathways for TGF-β to activate renal brosis has been addressed [24,25]. Together with our current ndings, the p38 and JNK inhibitors may provide a potential target in the treatment of GO [21][22][23][24][25].…”

“…Yu et al [22] proposed that TGF-β1 activated hepatic stellate cells via p38 and ERK pathways in liver brosis. Tian et al [23] reported the correlation of TGF-β1dependent p38 and ERK pathways with nickel oxide nanoparticle-induced pulmonary brosis.…”