Background Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions. Results TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes. Conclusions Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

BackgroundGold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40–50 nm) collapsed endothelial tight junctions and increased their paracellular permeability. Inhaled nanoparticles have gained significant attention due to their biodistribution in the brain; however, little is known regarding their role in cerebral edema. The present study investigated the expression of aquaporin 1 (AQP1) in the cerebral endothelial cell line, bEnd.3, stimulated by Au-NPs.ResultsWe found that treatment with Au-NPs induced AQP1 expression and increased endothelial permeability to water. Au-NP exposure rapidly boosted the phosphorylation levels of focal adhesion kinase (FAK) and AKT, increased the accumulation of caveolin 1 (Cav1), and reduced the activity of extracellular regulated protein kinases (ERK). The inhibition of AKT (GDC-0068) or FAK (PF-573228) not only rescued ERK activity but also prevented AQP1 induction, whereas Au-NP-mediated Cav1 accumulation remained unaltered. Neither these signaling molecules nor AQP1 expression responded to Au-NPs while Cav1 was silenced. Inhibition of ERK activity (U0126) remarkably enhanced Cav1 and AQP1 expression in bEnd.3 cells. These data demonstrate that Au-NP-mediated AQP1 induction is Cav1 dependent, but requires the repression on ERK activity. Mice receiving intranasally administered Au-NPs displayed cerebral edema, significantly augmented AQP1 protein levels; furthermore, mild focal lesions were observed in the cerebral parenchyma.ConclusionsThese data suggest that the subacute exposure of nanoparticles might induce cerebral edema, involving the Cav1 dependent accumulation on endothelial AQP1.

Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27Kip1 or the impairment in mitogenic signal transduction driven by the epidermal growth factor (EGF) and EGF receptor (EGFR). We found that the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a repressor of EGFR, was induced in the absence of AHR in vitro and in vivo. The LRIG1 tends to degrade via a proteasome dependent manner by interacting with AHR in wild-type cells. Either LRIG1 or a disintegrin and metalloprotease 17 (ADAM17) were accumulated in AHR-defective cells, consequently accelerating the degradation of EGFR, and attenuating the response to mitogenic stimulation. We also affirmed low AHR but high LRIG1 levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients. This might partially elucidate the sluggish tissue repairment and developing inflammation in COPD patients.

It was highlighted that the original article [1] contained the wrong Fig. 1.