Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling.

Microplastics (MPs) are environmental pollutants and can be inhaled by humans to threaten health. The lung tissue, responsible for the gas exchange between the body and the environment, is vulnerable to MPs exposure. However, from the perspective of cellular senescence, the effect of MPs on lung cells and tissues has not yet been deeply dissected. In this study, we reported that all the four typical MPs exhibited the significant biological effects in term of inducing senescence of human lung derived cells A549 and BEAS-2B in vitro. We further found that polyvinyl chloride (PVC) increased the reactive oxygen species (ROS) level in A549 cells and that PVC-induced senescent characteristics could be largely reversed by antioxidant treatment. Importantly, intratracheal instillation of PVC MPs in mice could effectively impair their physical function, induce the increased systemic inflammation level, cause the accumulation of senescent cells. Our study demonstrates that MPs induce senescence in human lung epithelial cells and mouse lungs by activating ROS signaling, and provides new insight into the potential pathogenesis of MPs on lung diseases.

Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo.

Embryonic stem cells (ESCs) are pluripotent stem cells derived from early stage embryos. It remains unclear whether inhibiting the Wnt/ß­catenin signaling pathway using dickkopf Wnt signaling pathway inhibitor 1 (DKK1) impacts on the differentiation potential of mouse ESCs in vitro and in vivo. In the present study, immunohistochemical staining was used to measure the expression of markers of the three germ layers in ESCs and teratomas derived from ESCs. The expression of markers for the Wnt/ß­catenin signaling pathway were detected by reverse transcription­polymerase chain reaction (RT­qPCR). Immunohistochemistry and western blotting indicated that the expression levels of octamer­binding transcription factor 4 in the DKK1­treated ESC group were significantly greater compared with the control ESCs. Reduced expression levels of NeuroD and bone morphogenetic protein 4 were observed in the DKK1­treated ESCs and teratomas derived from DKK1­treated ESCs compared with the control group. Increased expression levels of SOX17 were observed in the DKK1­treated ESCs compared with the control group. RT­qPCR indicated that ß­catenin expression was significantly reduced in DKK1­treated ESCs and teratomas derived from DKK1­treated ESCs compared with the control groups. Western blotting indicated no alterations in the expression of GSK­3ß, however, the levels of phosphorylated­GSK­3ß were significantly greater in the DKK1 treatment groups, while cyclin D1 and c­Myc expression levels were significantly reduced in the DKK1 treatment groups compared with the control groups. These results suggest that inhibiting Wnt signaling in ESCs using DKK1 may promote mouse ESCs to differentiate into endoderm in vitro and in vivo, and suppress the tumorigenicity of ESCs.