title: Reactive oxygen species-mediated p38 MAPK regulates carbon nanotube-induced fibrogenic and angiogenic responses.
abstract: Single-walled carbon nanotubes (SWCNTs) are fibrous nanoparticles that are being used widely for various applications including drug delivery. SWCNTs are currently under special attention for possible cytotoxicity. Recent reports suggest that exposure to nanoparticles leads to pulmonary fibrosis. We report that SWCNT-mediated interplay of fibrogenic and angiogenic regulators leads to increased angiogenesis, which is a novel finding that furthers the understanding of SWCNT-induced cytotoxicity. SWCNTs induce fibrogenesis through reactive oxygen species-regulated phosphorylation of p38 mitogen-activated protein kinase (MAPK). Activation of p38 MAPK by SWCNTs led to the induction of transforming growth factor (TGF)-β1 as well as vascular endothelial growth factor (VEGF). Both TGF-β1 and VEGF contributed significantly to the fibroproliferative and collagen-inducing effects of SWCNTs. Interestingly, a positive feedback loop was observed between TGF-β1 and VEGF. This interplay of fibrogenic and angiogenic mediators led to increased angiogenesis in response to SWCNTs. Overall this study reveals key signalling molecules involved in SWCNT-induced fibrogenesis and angiogenesis.
authors.affiliation: Department of Pharmaceutical Sciences, Hampton University, Hampton, VA 23668, USA.
authors.forename: Neelam
authors.initials: N
authors.lastname: Azad
authors.forename: Anand Krishnan V
authors.initials: AK
authors.lastname: Iyer
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongju
authors.initials: Y
authors.lastname: Lu
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D037742:Nanotubes, Carbon / Q000633:toxicity*; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress / Q000187:drug effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases