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Updated: Jul 17, 2025
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
USP25 ameliorates diabetic nephropathy by inhibiting TRAF6-mediated inflammatory responses
Baohua Liu1, Xiaomin Miao2, Jiangyun Shen3
1Department of Neurological Rehabilitation, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325027 Wenzhou, China.
Abstract:
Diabetic kidney disease (DKD) is a common diabetic vascular complication affecting nearly 40% of patients with diabetes. The lack of efficacious therapy for DKD necessitates the in-depth investigation of the molecular mechanisms underlying the pathogenesis and progression of DKD, which remain incompletely understood. Here, we discovered that the expression of USP25, a deubiquitinating enzyme, was significantly upregulated in the kidney of diabetic mice. Ablation of USP25 had no influence on glycemic control in type 1 diabetes but significantly aggravated diabetes-induced renal dysfunction and fibrosis by exacerbating inflammation in the kidney. In DKD, USP25 was mainly expressed in glomerular mesangial cells and kidney-infiltrating macrophages. Upon stimulation with advanced glycation end-products (AGEs), USP25 markedly inhibited the production of proinflammatory cytokines in these two cell populations by downregulating AGEs-induced activation of NF-κB and MAPK pathways. Mechanistically, USP25 interacted with TRAF6 and inhibited its K63 polyubiquitination induced by AGEs. Collectively, these findings identify USP25 as a novel regulator of DKD.
Insights
USP25, a deubiquitinating enzyme, is upregulated in diabetic kidney disease (DKD). Its absence worsens kidney dysfunction and fibrosis by increasing inflammation, revealing USP25 as a novel DKD regulator.
Area of Science:
- Nephrology
- Molecular Biology
- Endocrinology
Background:
- Diabetic kidney disease (DKD) affects 40% of diabetes patients.
- Understanding DKD pathogenesis is crucial for developing effective therapies.
- Molecular mechanisms of DKD progression are not fully understood.
Purpose of the Study:
- Investigate the role of USP25 in diabetic kidney disease.
- Elucidate the molecular mechanisms by which USP25 regulates DKD.
Main Methods:
- Utilized a mouse model of type 1 diabetes.
- Assessed USP25 expression in kidney tissue.
- Examined the impact of USP25 ablation on renal function and inflammation.
- Investigated USP25's interaction with TRAF6 and its effect on NF-κB and MAPK pathways.
Main Results:
- USP25 expression was significantly upregulated in the kidneys of diabetic mice.
- USP25 deficiency aggravated diabetes-induced renal dysfunction, fibrosis, and inflammation.
- USP25 inhibited AGEs-induced activation of NF-κB and MAPK pathways in mesangial cells and macrophages.
- USP25 interacted with TRAF6, inhibiting its K63 polyubiquitination.
Conclusions:
- USP25 acts as a protective factor against DKD progression.
- USP25 downregulates inflammatory pathways in DKD.
- USP25 is a novel therapeutic target for diabetic kidney disease.
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