Abstract: TH-PO208
CXCL5 Inhibition Attenuates Diabetic Kidney Disease in a Mouse Model of Type 2 Diabetes Mellitus
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Chang, Ting-Ting, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
- Chen, Ching, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan
- Chen, Jaw-Wen, Taipei Veterans General Hospital, Taipei, Taiwan
Background
Diabetic kidney disease (DKD) is typically characterized by progressive proteinuria and decreasing glomerular filtration rate, which might finally progress to end stage renal disease. Chemokines are critically involved in the inflammatory progression in the development of DN. CXC motif chemokine ligand 5 (CXCL5), a CXC type chemokine, is found upregulated in clinical and experimental diabetes mellitus (DM). Given the potential involvement of CXCL5 in the development or progression of DKD, this study sought to investigate the direct impacts of CXCL5 inhibition on DKD in experimental type 2 DM.
Methods
Leprdb/JNarl type 2 DM mice were used for a mouse model of DKD. Mice were randomly assigned to receive an anti-CXCL5 neutralizing monoclonal antibody or a control antibody for 4 weeks. Serum blood urea nitrogen (BUN), creatinine (Cre), and uric acid levels were examined before and after the treatment. Urinary albumin-to-creatinine ratio (UACR) and kidney-to-body weight ratio were measured. Renal glomerulosclerosis and fibrosis were also evaluated by Periodic acid-Schiff staining and Masson's trichrome staining after the treatment.
Results
Serum CXCL5 concentrations, body weight, and blood glucose levels were upregulated in the DKD mice. Serum BUN, Cre, and uric acid levels that were enhanced in DKD mice with a control antibody were decreased in mice treated with an anti-CXCL5 antibody. The UACR and kidney-to-body weight ratio were attenuated by the treatment of anti-CXCL5 antibodies compared to that of control antibodies. Furthermore, glomerular hypertrophy, glomerulosclerosis, and renal fibrosis were also reduced in DKD mice that received the anti-CXCL5 antibody.
Conclusion
Our pilot findings suggested that in vivo CXCL5 inhibition could improve renal function and reduce urinary albumin-to-creatinine ratios, glomerular hypertrophy, glomerulosclerosis, and renal fibrosis in DKD mice. The molecular mechanistic insights may be further explored to provide a novel theoretical basis for CXCL5 as a potential therapeutic target in DKD.