Cross regulation between hypoxia-inducible transcription factor-1α (HIF-1α) and transforming growth factor (TGF)-ß1 mediates nickel oxide nanoparticles (NiONPs)-induced pulmonary fibrosis.
Year: 2015
Type: article
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.
Source: PubMed Central
Institutions: Army Medical University, Southwest Hospital
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2416089547