Diabetic Nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Studies have indicated that Transforming Growth Factor beta1 (TGFβ1) is the most potent factor contributing to renal fibrosis, and understanding the exact pathogenic mechanism of renal fibrosis is crucial for alleviating the condition. Previous research has identified Yin Yang 1 (YY1) as an effective inhibitor of TGF-β1. Our study, through dual-luciferase reporter gene assays and Western blot experiments, screened and obtained the small molecule compound PdⅡ. Subsequently, validation in a high-glucose-induced renal mesangial cell injury model showed that PdⅡ treatment significantly increased the expression of YY1 protein and mRNA, while correspondingly reducing the expression of TGFβ1 protein and mRNA. Dual-luciferase reporter gene assay results revealed that, compared to the control group, the luciferase transcription activity of YY1 molecules increased in the PdⅡ treatment group, and the luciferase transcription activity of TGFβ1 decreased. By further designing mutations in the binding sites between TGFβ1 and YY1 on the promoter, transfecting fluorescent enzyme reporter gene plasmids with TGFβ1 mutant promoter into mesangial cells damaged by high glucose, and then treating the cells with PdⅡ, it was observed that the luciferase transcription activity of TGFβ1 did not decrease. Therefore, these results suggest that PdⅡ may inhibit TGFβ1 transcriptional activity by activating YY1, thereby slowing down the progression of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.metop.2024.100316 | DOI Listing |
Cell Signal
January 2025
School of Basic Medicine, Jiamusi University, Jiamusi 154007, PR China. Electronic address:
The possible involvement of mTOR/p70S6K signaling in mediating Fibrillin-1 expression during the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A CA/CPR AKI model was established using male C57BL/6 mice aged 8-12 weeks. The expression of Fibrillin-1 and activation of the mTOR/p70S6K signaling pathway in kidney tissues were assessed at different time points.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the development of renal fibrosis. Eliminating senescent TECs has been proven to effectively reduce renal fibrosis.
View Article and Find Full Text PDFTransplant Direct
March 2024
Department of Nephrology, Odense University Hospital, Odense, Denmark.
Background: Kidney fibrosis is a suggested cause of kidney failure and premature mortality. Because collagen type VI is closely linked to kidney fibrosis, we aimed to evaluate whether urinary endotrophin, a collagen type VI fragment, is associated with graft failure and mortality among kidney transplant recipients (KTR).
Methods: In this prospective cohort study, KTR with a functioning graft ≥1-y posttransplantation were recruited; 24-h urinary endotrophin excretion was measured using an ELISA method.
Front Pharmacol
January 2025
Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Renal fibrosis is one of the main pathological features of chronic kidney disease (CKD), and its treatment has been a hot research topic. Recent studies have shown that stem cell therapy can repair renal pathological changes and slow the progression of CKD. In addition, a large number of experiments have confirmed that traditional Chinese medicine (TCM), especially Chinese medicine compound preparations, has the advantage of multitargeting interventions to improve renal fibrosis.
View Article and Find Full Text PDFFront Bioeng Biotechnol
January 2025
Department of Urology, Beilun People's Hospital, Ningbo, Zhejiang, China.
Renal ischemia-reperfusion (IR) induces tissue hypoxia, resulting in disrupted energy metabolism and heightened oxidative stress. These factors contribute to tubular cell damage, which is a leading cause of acute kidney injury (AKI) and can progress to chronic kidney disease (CKD). The excessive generation of reactive oxygen species (ROS) plays a crucial role in the pathogenesis of AKI.
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