Nickel oxide nanoparticles induced pulmonary fibrosis via TGF- β1 activation in rats.
Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200-240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
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XH
Chang
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
A
A
Zhu
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
F F
FF
Liu
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
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LY
Zou
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
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L
Su
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
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SK
Liu
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
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Zhou
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
Y Y
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Sun
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
A J
AJ
Han
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
Y F
YF
Sun
2 Lanzhou Municipal Center for Disease Control, Lanzhou, China.
S
S
Li
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
J
J
Li
1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.
Y B
YB
Sun
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D009532:Nickel; C028007:nickel monoxide
Nanoparticle; TGF-β1; collagen; nickel oxide; pulmonary fibrosis