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Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1.

ABSTRACT: Exposure to multi-walled carbon nanotubes (MWCNTs) is suspected to contribute to pulmonary fibrosis through modulation of transforming growth factor beta1 (TGF-?1). There is growing evidence that estrogen signaling is important in pulmonary function and modulates pro-fibrogenic signaling in multiple models of pulmonary fibrosis, however an interaction between MWCNT exposure and estrogen signaling in the lung is not known. The purpose of this work was to determine whether estrogen signaling in the lung is a target for MWCNTs and to identify potential signaling mechanisms mediating MWCNT-induced responses using a whole-body inhalation mouse model and an in vitro human lung cell model. Mice exposed to MWCNTs had reduced mRNA expression of estrogen receptor alpha and beta (Esr1 and Esr2, respectively) in lung tissue at multiple time-points post-exposure, whereas expression of g-protein coupled estrogen receptor1 (Gper1) was more variable. We localized ESR1 protein expression as primarily associated with bronchioles and within inflammatory macrophages. The reduction in estrogen receptor expression was concomitant to an increase in TGF-?1 levels in the bronchoalveolar lavage fluid (BALF) of MWCNT-exposed animals. We confirmed a role for TGF-?1 in mediating MWCNT-induced repression of ESR1 mRNA expression using a TGF-? type-I receptor inhibitor in bronchial epithelial cells in vitro. Overall these results highlight a novel mechanism of MWCNT-induced signaling where MWCNT-induced regulation of TGF-?1 represses estrogen receptor expression. Dysregulated estrogen signaling through altered receptor expression may have potential consequences on lung function.

SUBMITTER: Smith LC

PROVIDER: S-EPMC7169977 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1.

Smith L Cody LC Moreno Santiago S Robinson Sarah S Orandle Marlene M Porter Dale W DW Das Dipesh D Saleh Navid B NB Sabo-Attwood Tara T

NanoImpact 20190201

Exposure to multi-walled carbon nanotubes (MWCNTs) is suspected to contribute to pulmonary fibrosis through modulation of transforming growth factor beta1 (TGF-β1). There is growing evidence that estrogen signaling is important in pulmonary function and modulates pro-fibrogenic signaling in multiple models of pulmonary fibrosis, however an interaction between MWCNT exposure and estrogen signaling in the lung is not known. The purpose of this work was to determine whether estrogen signaling in th ...[more]

PMID: 32313843

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Project description:The studies focusing on magnesium oxychloride cement (MOC) composites have recently become fairly widespread because of MOC's excellent mechanical properties and environmental sustainability. Numerous fillers, admixtures and nano-dopants were studied in order to improve the overall performance of MOC-based derivatives. Some of them exhibited specific flaws, such as a tendency to aggregate, increase in porosity, aeration of the composite matrix, depreciation in water resistance and mechanical strength, etc. In this manuscript, MOC-based composites doped by multi-walled carbon nanotubes (MWCNTs) are designed and tested. In order to modify the final properties of composites, diatomite was admixed as partial substitution of MgO, which was used in the composition of the researched material in excess, i.e., the majority of MgO constituted part of MOC and the rest served as fine filler. The composites were subjected to the broad experimental campaign that covered SEM (scanning electron microscopy), EDS (energy dispersive spectroscopy), HR-TEM (high-resolution transmission electron microscopy), XRD (X-ray diffraction), OM (optical microscopy) and STA-MS (simultaneous thermal analysis with mass spectroscopy). For 28 days hardened samples, macrostructural and microstructural parameters, mechanical properties, hygric and thermal characteristics were experimentally assessed. The incorporation of MWCNTs and diatomite resulted in the significant enhancement of composites' compactness, mechanical strength and stiffness and reduction in water absorption and rate of water imbibition. The thermal properties of the enriched MOC composites yielded interesting values and provided information for future modification of thermal performance of MOC composites with respect to their specific use in practice, e.g., in passive moderation of indoor climate. The combination of MWCNTs and diatomite represents a valuable modification of the MOC matrix and can be further exploited in the design and development of advanced building materials and components.

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Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1.

Publications

Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1.

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