Nano-sized microplastics exposure induces skin cell senescence via triggering the mitochondrial localization of GSDMD

纳米级微塑料暴露通过触发 GSDMD 的线粒体定位诱导皮肤细胞衰老

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作者:Wang Han, Jiayue Cui, Gao Sun, Xiao Miao, Zhang Pufang, Li Nannan

Abstract

Nano-sized microplastic pollution is distributed worldwide. Nano-sized microplastics can enter the blood through the digestive tract, and then transported to various tissues and organs of the body, resulting in a series of toxicological effects. In addition, nano-sized microplastics can penetrate the skin barrier. However, the toxicological effects of nano-sized microplastics on the skin are still not completely understood. Two skin cell lines were used as in vitro models to investigate the toxicological effects of nano-sized microplastics on skin cells and their potential molecular mechanisms. First, cellular behavioral research results showed that nano-sized microplastics can be internalized into skin cells in a time- and dose-dependent manner. Further experiments using western blotting, indirect immunofluorescence, and ELISA assays demonstrated that nano-sized microplastics cause an increase in skin cell inflammation levels. Additionally, our research showed that nano-sized microplastics caused skin cell senescence damage by evaluating aging-marker molecules such as p16 and p21. Subsequently, we studied the potential molecular mechanism by which nano-sized microplastics cause pathological skin injury and found that they induce mitochondrial oxidative stress, depolarize the mitochondrial membrane potential, and recruit GSDMD to the mitochondria. Subsequently, mtDNA enters the cytoplasm via GSDMD pores, which then activates the AIM2 Inflammasome. Ultimately, it causes a series of biochemical reactions such as inflammation and aging in cells. In an in vivo model, we tested the effect of nano-sized microplastics on skin regeneration and found that they acted as an inhibitor to skin regeneration and aggravated the inflammatory reaction of the skin. Overall, our results provide new evidence of the skin toxicity of nano-sized microplastics. This study provides a theoretical foundation for further research on the potential toxicological effects of nano-sized microplastics on the skin.

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