In the process of renal fibrosis, intrinsic renal cells are damaged due to the pathogenic factors, leading to increased collagen deposition, resulting in gradual sclerosis of renal parenchyma, scarring, and a loss of basic metabolic function, causing end-stage kidney disease (ESKD). 2 Alleviating renal tissue injury and renal dysfunction is a great challenge faced by clinicians and researchers. 1 Since renal failure is progressive and irreversible and there is a lack of specific drugs to protect renal function, the quality of life of patients with CKD is threatened and it burdens the patients’ families and the society economically. The prevalence of CKD is 8%-16% worldwide.
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Keywords: Suyin Detoxification Granule, renal tubular epithelial cells, mitochondrial dysfunction, MAVS, NLRP3 inflammasome, pyroptosis, EMTĬhronic kidney disease (CKD) is an increasingly serious public health problem.
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The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis.Ĭonclusion: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. Results: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Methods: Firstly, the rat model of renal failure was established using intragastric administration of adenine. However, the underlying mechanism is still unknown. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Purpose: Proteinuria is an independent risk factor of chronic kidney disease (CKD). 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China 3Zou’s Nephrology Medicine Intangible Cultural Heritage Inheritance Studio, Nanjing Boda Nephrology Hospital, Nanjing, Jiangsu, People’s Republic of China 4Inheritance Studio of Traditional Chinese Medicine Master Yanqin Zou, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaĬorrespondence: Enchao Zhou Yanqin Zou Tel +86-13851572603Įmail
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Yiye Zhu, 1, 2 Guoshun Huang, 1, 2 Yang Yang, 1, 2 Chen Yong, 1, 2 Xiang Yu, 1, 2 Gang Wang, 3 Lan Yi, 1, 4 Kun Gao, 1, 4 Fang Tian, 2 Shushu Qian, 2 Enchao Zhou, 1, 4 Yanqin Zou 1, 3, 4ġDepartment of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China 2No.