PMID- 38382346 OWN - NLM STAT- MEDLINE DCOM- 20240318 LR - 20240318 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 273 DP - 2024 Mar 15 TI - PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-beta1/Smad2/3 signaling pathways. PG - 116102 LID - S0147-6513(24)00177-5 [pii] LID - 10.1016/j.ecoenv.2024.116102 [doi] AB - 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. 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 microm PS-MPs) and an H(2)O 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta), 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-beta/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. 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-beta1/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. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Feng, Lixiang AU - Feng L AD - Department of Urology, Wuhan Third Hospital, School of Medicine, Wuhan University of Science and Technology, Wuhan 430060, China. FAU - Chen, Chen AU - Chen C AD - Department of Urology, Wuhan Third Hospital, School of Medicine, Wuhan University of Science and Technology, Wuhan 430060, China. FAU - Xiong, Xi AU - Xiong X AD - Department of Urology, Wuhan Third Hospital, Wuhan University, Wuhan 430060, China. FAU - Wang, Xiong AU - Wang X AD - Department of Pharmacy, Wuhan Third Hospital, Wuhan 430060, China. FAU - Li, Xinxin AU - Li X AD - Department of Urology, Wuhan Third Hospital, Wuhan University, Wuhan 430060, China. FAU - Kuang, Qihui AU - Kuang Q AD - Department of Urology, Wuhan Third Hospital, Wuhan University, Wuhan 430060, China. FAU - Wei, Xiao AU - Wei X AD - Department of Urology, Wuhan Third Hospital, Wuhan University, Wuhan 430060, China. FAU - Gao, Likun AU - Gao L AD - Department of Pathology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University, Shenzhen 518020, China. FAU - Niu, Xuan AU - Niu X AD - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, China. FAU - Li, Qingwen AU - Li Q AD - Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. FAU - Yang, Jun AU - Yang J AD - Department of Urology, Wuhan Third Hospital, Wuhan 430060, China. Electronic address: 735291410@qq.com. FAU - Li, Lili AU - Li L AD - Central Laboratory, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: 26061047@qq.com. FAU - Luo, Pengcheng AU - Luo P AD - Department of Urology, Wuhan Third Hospital, School of Medicine, Wuhan University of Science and Technology, Wuhan 430060, China. Electronic address: pluo@whu.edu.cn. LA - eng PT - Journal Article DEP - 20240221 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Transforming Growth Factor beta1) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Microplastics) RN - 0 (Polystyrenes) RN - 0 (NLR Proteins) RN - EC 3.4.22.36 (Caspase 1) RN - 0 (Blood Glucose) RN - 0 (Plastics) SB - IM MH - Mice MH - Animals MH - *Diabetic Nephropathies MH - Transforming Growth Factor beta1/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Microplastics/metabolism MH - Polystyrenes/metabolism MH - NLR Proteins MH - Caspase 1/metabolism MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - Plastics/metabolism MH - Kidney MH - Signal Transduction MH - Inflammation/metabolism MH - Fibrosis OTO - NOTNLM OT - Diabetic nephropathy OT - Kidney injury OT - Microplastics OT - NLRP3 inflammasome OT - db/db mice COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/22 00:42 MHDA- 2024/03/18 06:42 CRDT- 2024/02/21 18:10 PHST- 2023/10/27 00:00 [received] PHST- 2024/02/05 00:00 [revised] PHST- 2024/02/08 00:00 [accepted] PHST- 2024/03/18 06:42 [medline] PHST- 2024/02/22 00:42 [pubmed] PHST- 2024/02/21 18:10 [entrez] AID - S0147-6513(24)00177-5 [pii] AID - 10.1016/j.ecoenv.2024.116102 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2024 Mar 15;273:116102. doi: 10.1016/j.ecoenv.2024.116102. Epub 2024 Feb 21.