LncRNA MEG3 Involved in NiO NPs-Induced Pulmonary Fibrosis via Regulating TGF-β1-Mediated PI3K/AKT Pathway
| Autor: | Xiaoxia Wang, Haibing Zhan, Xingchang Sun, Jinfa Zheng, Xuefeng Gong, Qing Gao, Han Liu, Xuhong Chang, Mengmeng Yang, Yingbiao Sun, Sanwei Feng |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pulmonary Fibrosis Toxicology Transforming Growth Factor beta1 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Pulmonary fibrosis medicine Animals Humans LY294002 Rats Wistar PI3K/AKT/mTOR pathway A549 cell Phosphoinositide 3-kinase biology Chemistry Akt/PKB signaling pathway respiratory system medicine.disease Molecular biology Rats Fibronectin 030104 developmental biology 030220 oncology & carcinogenesis Transforming Growth Factors biology.protein RNA Long Noncoding Phosphatidylinositol 3-Kinase Proto-Oncogene Proteins c-akt Type I collagen |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology. 182(1) |
| ISSN: | 1096-0929 |
| Popis: | Long noncoding RNA maternally expressed gene 3 (MEG3) involves in fibrotic diseases, but its role in nickel oxide nanoparticles (NiO NPs)-induced pulmonary fibrosis remains unclear. The present study aimed to explore the relationships among MEG3, transforming growth factor-β1 (TGF-β1) and phosphoinositide 3-kinase (PI3K)/AKT pathway in NiO NPs-induced pulmonary fibrosis. Wistar rats were intratracheally instilled with NiO NPs twice a week for 9 weeks, and human lung adenocarcinoma epithelial cells (A549 cells) were exposed to NiO NPs for 24 h. The pathological alterations and increased hydroxyproline indicated that NiO NPs caused pulmonary fibrosis in rats. The up-regulated type I collagen (Col-I) suggested that NiO NPs-induced collagen deposition in A549 cells. Meanwhile, NiO NPs could significantly down-regulate MEG3, up-regulate TGF-β1 and activate PI3K/AKT signaling pathway both in vivo and in vitro. However, we found that the PI3K/AKT pathway activated by NiO NPs could be suppressed by 10 μM TGF-β1 inhibitor (SB431542) in A549 cells. The protein markers (Col-I, Fibronectin, and alpha-smooth muscle actin) of collagen deposition up-regulated by NiO NPs were reduced by 10 μM PI3K inhibitor (LY294002). Furthermore, we further found that overexpressed MEG3 inhibited the expression of TGF-β1, resulting in the inactivation of PI3K/AKT pathway and the reduction of collagen formation. In summary, our results validated that MEG3 could arrest NiO NPs-induced pulmonary fibrosis via inhibiting TGF-β1-mediated PI3K/AKT pathway. |
| Databáze: | OpenAIRE |
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