title: Cross regulation between hypoxia-inducible transcription factor-1α (HIF-1α) and transforming growth factor (TGF)-ß1 mediates nickel oxide nanoparticles (NiONPs)-induced pulmonary fibrosis.
abstract: Numerous analyses including in vivo and in vitro experiments have demonstrated that inhalation exposure of NiONPs can result in pulmonary fibrosis. However, the potential mechanisms of this pathological process remain elusive. Here, we investigate the role of HIF-1α and TGF-ß1 in NiONPs-induced pulmonary fibrosis with a focus on the interplay of the above two proteins. In vivo, male Sprague&Dawley rats were exposed to NiONPs and pulmonary fibrosis was demonstrated using H&E staining and immunochemistry of αSMA. In vitro, NiONPs contributed to cell proliferation and increased expressions of collagen-1 and αSMA in human fetal lung fibroblasts. Both HIF-1α and TGF-ß1 were upregulated by NiONPs treatment. Inhibition of HIF-1α reduced TGF-ß1 expression and downregulation of TGF-ß1 reduced HIF-1α protein level. Mechanism investigation revealed that TGF-ß1 affects nuclear translocation activity of HIF-1α. Taken together, these finding provide evidence that HIF-1α and TGF-ß1 act in synergy to foster NiONPs-induced pulmonary fibrosis, and the cross talk between them is a pivotal mechanism of pulmonary fibrosis.
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical UniversityChongqing 400038, China; Department of Occupational Health, Third Military Medical UniversityChongqing 400038, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Mindi
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Weixia
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Occupational Health, Third Military Medical University Chongqing 400038, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Southwest Hospital, Third Military Medical University Chongqing 400038, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
keywords: Nanoparticles; hypoxia; transforming growth factor