Abstract: SA-PO241
Nuclear Receptor Coactivator 3 Deficiency Damages Podocyte Injury Through Targeting Fyn/AMPK/mTOR Signaling Pathway
Session Information
- Diabetic Kidney Disease: Basic - II
November 05, 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
Author
- Yaru, Xie, Wuhan Union Hospital Department of Neurology, Wuhan, Hubei, China
Background
Diabetic kidney disease (DKD) is one of the most common chronic complications of diabetes and has become the main cause of end-stage renal disease. Podocytes, the visceral epithelial cells of the renal capsule, adhere to the outer surface of the glomerular basement membrane (GBM), and form the glomerular filtration barrier with vascular endothelial cells and GBM.Podocytes are terminally differentiated cells that cannot efficiently proliferate and renew after damage. Therefore, once the podocytes are damaged to a certain extent, it will lead to damaged capillary loops and glomerulosclerosis. It is well known that high glucose is closely related to intercellular interactions and apoptosis of podocytes. However, the exact mechanism in high glucose-mediated podocyte injury has not been fully elucidated. Therefore, the study of podocyte injury and protection mechanisms is the key to the treatment of DKD.
Methods
C57 male mice were injected with STZ intraperitoneally to establish a diabetic nephropathy model, and the changes of NCOA3 and downstream indicators Fyn/AMPK/mTOR/autophagy were detected; at the same time, podocytes were stimulated with high glucose to verify the changes of the above indicators in vitro. The NCOA3 podocyte-specific knockout mice were constructed and STZ was injected . The blood and urine biochemical levels, renal pathological changes and the downstream indicators of Fyn/AMPK/mTOR/autophagy were detected. C57 male mice were injected with NCOA3 overexpressing virus via tail vein and intraperitoneally injected with STZ to establish a diabetic nephropathy model. Biochemical levels of blood and urine, renal pathological changes and downstream indicators of Fyn/AMPK/mTOR/autophagy were detected.
Results
This study found that NCOA3 expression was down-regulated in DKD. Knockout of NCOA3 in renal podocytes leads to renal pathological changes in mice, and upregulation of NCOA3 promotes the Fyn/AMPK/mTOR/autophagy pathway to inhibit the progression of diabetic nephropathy
Conclusion
The current findings suggest that NCOA3 is a key molecule in the development of diabetic nephropathy. NCOA3 can activate autophagy, thereby inhibiting disease progression, providing new ideas and targets for the treatment of diabetic nephropathy.