Exploring the Role of CXCL16 in Diabetic Kidney Disease: Insights into Inflammation, Lipid Disorders, and Therapeutic Potential of Curcumin
- Diabetic Kidney Disease: Basic - II
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
- Cao, Aili, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Chen, Ying, Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine,, Shanghai, China
- Tao, Jun, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Hou, Xudong, Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Diabetic nephropathy (DN) is a common complication of diabetes characterized by the progressive presence of albumin in the urine and the destruction of glomeruli. Elevated levels of soluble C-X-C chemokine ligand 16 (CXCL16) have been associated with inflammatory and lipid responses, which play a significant role in the development of renal dysfunction in patients with diabetes. However, the precise mechanisms through which CXCL16 affects DN are not yet fully understood.
To address this, we conducted a comprehensive study to investigate how CXCL16 contributes to podocyte injury in DN.
CXCL16 were associated with abnormal lipid metabolism. The addition of CXCL16 to podocytes led to the formation of lipid droplets, along with increased expression involved in lipid synthesis and storage. CXCL16 treatment inhibited the movement of Nrf2 into the nuclei of podocytes. To explore potential therapeutic approaches, we evaluated the effects of curcumin, a compound known to activate Nrf2, on podocyte senescence and injury. Our results demonstrated that curcumin treatment reduced the accumulation of lipid droplets and mitigated podocyte injury, as evidenced by a decrease in cellular senescence. Importantly, we found that the protective effects of curcumin were inhibited when CXCL16 was reduced by CXCL16 siRNA. Meanwhile, curcumin treatment prevented CXCL16-induced oxidative stress and inflammation, preserved the expression of synaptopodin, and inhibited the abnormal movement of Nrf2. Through molecular modeling and docking analysis, we discovered that curcumin directly targeted a specific region in the CXCL16 protein, blocking its kinase activity. In a mouse model of DN, we validated the therapeutic potential of curcumin.
Taken together, our findings suggest that CXCL16 may serve as a promising therapeutic target for the treatment of DKD.