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Isolation, Characterization, And High Throughput Extracellular Flux Analysis of Mouse Primary Renal Tubular Epithelial Cells
Published on: June 20, 2018
Polystyrene microplastics facilitate renal fibrosis through accelerating tubular epithelial cell senescence
Chun Pan1, Xinglong Wang2, Zhencheng Fan1
1Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
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.
Insights
Microplastics exposure harms kidney function, increasing serum markers and causing inflammation and fibrosis. Restoring Klotho function may mitigate these microplastic-induced renal effects.
Area of Science:
- Environmental Science
- Toxicology
- Nephrology
Background:
- Microplastics (MPs) are emerging contaminants found in the kidney, raising concerns about renal toxicity.
- Kidney susceptibility to MPs is suggested by their transport and enrichment within renal tissues.
Purpose of the Study:
- To investigate the renal toxicity of different types of microplastics (unmodified, negatively charged, and positively charged polystyrene) in a mouse model.
- To elucidate the mechanisms underlying microplastic-induced kidney damage, focusing on inflammation, fibrosis, and cellular senescence.
- To identify the role of the Klotho/Wnt/β-catenin signaling pathway in microplastic nephrotoxicity.
Main Methods:
- Administration of various microplastics to mice for 28 days at human-equivalent concentrations.
- Analysis of serum and urine markers for kidney injury, including urea nitrogen (BUN), creatinine (CREA), uric acid (UA), protein, and microalbumin.
- Histopathological examination of kidney tissues to assess inflammation, fibrosis, and cellular senescence.
- Investigation of the Klotho/Wnt/β-catenin signaling pathway and its role in microplastic-induced renal pathology.
Main Results:
- Microplastic exposure significantly elevated serum BUN, CREA, UA, and urinary protein and microalbumin.
- MPs induced persistent kidney inflammation and fibrosis, linked to increased tubular epithelial cell senescence.
- The Klotho/Wnt/β-catenin pathway was identified as critical in MP-induced cell senescence and epithelial-mesenchymal transition.
- MPs promoted TGF-β1 secretion from senescent cells, activating renal fibroblasts, which was reversed by restoring Klotho function.
Conclusions:
- Microplastics cause significant kidney damage, including inflammation and fibrosis, mediated by cellular senescence and the Klotho/Wnt/β-catenin pathway.
- The findings highlight a novel link between microplastic pollution and renal fibrosis, contributing to understanding the health impacts of plastic.
- Restoring Klotho function presents a potential therapeutic strategy to counteract microplastic-induced kidney damage.
