Abstract

Pulmonary fibrosis is a poorlyunderstood pathologic condition. Carbon nanotubes (CNTs) are nanomaterials withpotentials for broad applications. CNTs can induce pulmonary fibrosis inanimals, a cause for concern for exposed workers and consumers. Giventhe large number of CNTs available on the market and the seemingly infinitenumber of ways these particles can be modified in ways that may affecttoxicity, in vitro models that can be used to quickly and effectively investigatethe relative fibrogenicity of CNTs are much needed. Here we analyzed thefibrogenic potentials of six CNTs of varying physical properties, as well ascrystalline silica, using two and three‐dimensional (2D and 3D, respectively) in vitro models. WI38‐VA13 human pulmonary fibroblasts were treated with CNTs orsilica, with TGF‐β1, a known inducer of fibroblastdifferentiation, as positive control. The cells were examined for fibroticmatrix alterations, including myofibroblast transformation, matrix remodeling, and matrix contraction. While all tested CNTs induced myofibroblastdifferentiation in 2D and 3D cultures, the 3D culture allowed the examinationof myofibroblast clustering, collagen deposition and rearrangement, celldivision, and matrix contraction in response to fibrogenic exposures, processescritical for fibrosis in vivo. At 1 μg/ml, multi‐walled carbon nanotubes (MWCNTs) elicit higherinduction of myofibroblast differentiation and matrix remodeling than single‐walledcarbon nanotubes (SWCNTs). Among MWCNTs, those with the highest and lowestaspect ratios produced the largest effects, which were comparable to those byTGF‐β1 and higher than those by silica. Thus, the 3D collagen‐based modelenables the study of matrix fibrotic processes induced by CNTs and silicaparticles directly and effectively. This in vitro approach to analyzingfibrogenic activities of inducers is applicable to a variety of fibrogenicagents including particles, fibers, nanomaterials, and soluble inducers.Support or Funding InformationSupported by a grant for Q.M. from the Health Effects Laboratory Division and the Nanotechnology Research Center at National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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