PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-β1/Smad2/3 signaling pathways

PS-MPs通过NLRP3/Caspase-1和TGF-β1/Smad2/3信号通路促进糖尿病肾病炎症和纤维化进展

阅读:10
作者:Lixiang Feng, Chen Chen, Xi Xiong, Xiong Wang, Xinxin Li, Qihui Kuang, Xiao Wei, Likun Gao, Xuan Niu, Qingwen Li, Jun Yang, Lili Li, Pengcheng Luo

Background

Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles.

Conclusion

The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-β1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.

Methods

In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5 µm PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis.

Results

The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-β/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。