Abstract：
Microplastics (MPs), emerging contaminants, are easily transported and enriched in the kidney, suggesting the kidney is susceptible to the toxicity of MPs. In this study, we explored the toxicity of MPs, including unmodified polystyrene (PS), negative-charged PS-SO3H, and positive-charged PS-NH2 MPs, in mice models for 28 days at a human equivalent concentration. The results showed MPs significantly increased levels of UREA, urea nitrogen (BUN), creatinine (CREA), and uric acid (UA) levels in serum and white blood cells, protein, and microalbumin in urine. In the kidney, MPs triggered persistent inflammation and renal fibrosis, which was caused by the increased senescence of tubular epithelial cells. Moreover, we identified the critical role of the Klotho/Wnt/β-catenin signaling pathway in the process of MPs induced senescence of tubular epithelial cells, promoting the epithelial-mesenchymal transformation of epithelial cells. MPs supported the secretion of TGF-β1 by senescent epithelial cells and induced the activation of renal fibroblasts. On the contrary, restoring the function of Klotho can alleviate the senescence of epithelial cells and reverse the activation of fibroblasts. Thus, our study revealed new evidence between MPs and renal fibrosis, and adds an important piece to the whole picture of the plastic pollution on people\'s health.
摘要：
微塑料（MPs），新兴污染物，很容易在肾脏中运输和富集，提示肾脏易受MP的毒性。在这项研究中,我们探索了MPs的毒性，包括未改性聚苯乙烯(PS)，带负电荷的PS-SO3H,和带正电荷的PS-NH2议员，在小鼠模型中在人类等效浓度下28天。结果显示，MPs显著增加了UREA的水平，尿素氮（BUN），肌酐（CREA），血清和白细胞中的尿酸（UA）水平，蛋白质，和尿中的微量白蛋白.在肾脏，MPs引发持续性炎症和肾纤维化，这是由肾小管上皮细胞衰老增加引起的。此外，我们确定了Klotho/Wnt/β-catenin信号通路在MPs诱导的肾小管上皮细胞衰老过程中的关键作用,促进上皮细胞的上皮-间质转化。MPs支持衰老上皮细胞分泌TGF-β1并诱导肾成纤维细胞活化。相反,恢复Klotho的功能可以减轻上皮细胞的衰老并逆转成纤维细胞的活化。因此，我们的研究揭示了MPs与肾纤维化之间的新证据，并为整个塑料污染对人们健康的影响增加了重要的一块。
