Abstract 619P
Background
In recent years, the environmental health issue of microplastics has aroused increasingly greater source of concern. Some studies suggested that exposure to polystyrene microplastics (PS-MPs) may lead to renal inflammation and oxidative stress in animals. However, there is little known about the essential effects of PS-MPs with high-fat diet (HFD) on the renal development and microenvironment.
Methods
In this study, we provided the single-cell transcriptomic landscape of the kidney injury and immune cells population induced by PS-MPs and HFD in mouse model by unbiased single-cell RNA sequencing (scRNA-seq).
Results
showed that PS-MPs could accumulate in kidney, and PS-MPs exposure with HFD treatment largely reshape cellular components in mouse kidneys. First, we found that PS-MPs act on renal epithelial cells, specifically the proximal and distal convoluted tubule cells, to exacerbate the kidney burden induced by HFD, and promote MAPK and PARP signaling pathways. Second, PS-MPs exposure and and HFD treatment indicated activated oxidative phosphorylation and reactive oxygen species (ROS) mediated chemical carcinogenesis of mural cells. Besides, PS-MPs exposure markedly increased activation and proliferation of effective T cells, and down-regulated B cells activation. Meanwhile, PS-MPs exposure prominently increased the level of macrophages infiltration in mononuclear phagocytes, especially up-regulated the pro-inflammatory CXCL2+ macrophages and M2-like PF4+ macrophages subpopulation, which participated in the lysosome and ROS-mediated chemical carcinogenesis. Multispectral immunofluorescence and immunohistochemistry identified PF4+ macrophages in samples with human tumor-adjacent kidney and renal cell carcinoma. The activation of PF4+ macrophages mainly interacted with fibroblasts and injured renal tubular cells, and promoted the fibrosis process after renal injury.
Conclusions
In conclusion, this study systematically revealed molecular variation of both renal cells and immune cells in mice kidney microenvironment induced by PS-MPs and HFD, which provided a molecular basis for understanding the genitourinary injury mechanism of PS-MPs in mammals.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.
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