Abstract: TH-PO682
Reduced C/EBP-α Expression Aggravates the Podocyte Impairment and Renal Injury in Experimental Diabetes
Session Information
- Diabetes Mellitus and Obesity: Basic - Experimental - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Diabetes
- 501 Diabetes Mellitus and Obesity: Basic - Experimental
Authors
- Zhang, Liwen, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhou, Fangfang, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Liu, Jian, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Ying, Ji, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wang, Weiming, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Chen, Nan, Ruijin Hospoital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
CCAAT/enhancer binding protein-α (C/EBP-α) is one of the critical transcription factors involved in inflammation, cell proliferation and lipid metabolism. We have previously showed that C/EBP-α expression was suppressed in glomerular cells in focal segmental glomerulosclerosis. However, its specific role in diabetic nephropathy (DN) is unclear. We developed a podocyte-specific C/EBP-α-null mouse model to study the function of C/EBP-α in DN progression.
Methods
By crossing floxed C/EBP-α mice with Pod-Cre mice, we generated podocyte specific C/EBP-α knockout mice. The transgenic mice and their wild-type littermates underwent either high-fat diet for 6 months with a single injection of streptozotocin as diabetic models or general diet as control.
Results
We confirmed that C/EBP-α expression was significantly reduced in the renal cortex in podocyte-specific knockout mice by western blotting. Genetic ablation of C/EBP-α in podocytes led to more serious deterioration of diabetic kidney injuries, characterized by increased urinary albumin-to-creatinine ratio, increased mesangial matrix expansion, glomerulosclerosis and tubulointerstitial fibrosis (determined by Mason’s trichrome and Picrosirius Red stains). Diabetes induced down-regulation in the expression of podocyte and epithelial markers such as nephrin, podocin and E-cadherin, and these markers were further reduced in C/EBP-α knockout diabetic mice. In addition, a further increased expression of markers of fibrosis (vimentin, fibronectin) and inflammation (MCP-1, TNF-α) were found in diabetic C/EBP-α knockout mice when compared to diabetic WT mice. Mechanistically, we identified that conditional deletion of C/EBP-α in podocytes resulted in significantly decreased p-AMPK and PGC-1α expression in diabetic mice.
Conclusion
These findings suggest that knockdown of C/EBP-α expression in podocytes aggravates the podocyte impairment and the progressing of DN, and point to C/EBP-α as a potential therapeutic target in DN.
Funding
- Government Support - Non-U.S.