Osteopontin enhances multi-walled carbon nanotube-triggered lung fibrosis by promoting TGF-β1 activation and myofibroblast differentiation.

摘要: Carbon nanotubes (CNTs) have been used in a variety of applications because their unique properties and functions. However, many CNTs shown to induce lung fibrosis experimental animals with some at potency greater than that silica, raising concern over possible toxic effects CNT exposure humans. Research into the mechanisms by which pulmonary is warranted order facilitate understanding, monitoring, treatment CNT-induced lesions might occur exposed populations. The current study focuses on investigating role osteopontin (OPN) development upon multi-walled carbon (MWCNTs). C57BL/6J (WT) Opn knockout (KO) mice were MWCNTs pharyngeal aspiration examine acute chronic MWCNT exposure. OPN its mode action analyzed cellular molecular levels vivo vitro. was highly persistently induced both phases response mouse lungs. Comparison between WT KO revealed critically regulated MWCNT-induced as indicated reduced fibrotic focus formation myofibroblast accumulation At level, promotes expression activation TGF-β1, stimulates differentiation myofibroblasts from fibroblasts, increases production fibrous matrix proteins lungs cultured cells MWCNTs. CNT-exposed plays critical roles TGF-β1 signaling promote This reveals an OPN-dependent mechanism fibrosis. findings raise possibility using biomarker monitor drug target halt development.