Abstract: FR-PO203
The COX 2-Thromboxane Axis Plays a Critical Role in Podocyte Injury Induced by High Glucose
Session Information
- Diabetic Kidney Disease: Basic - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Song, Shicong, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Cheng, Wang, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
Background
Podocyte injury is a vital factor in the onset and progression of diabetic nephropathy (DN), thus is a promising therapeutic target to prevent DN. The cyclooxygenase 2 (COX 2)- thromboxane axis has been proved to play a critical role in podocyte injury whereas the underlying mechanism is still unknown. The aim of this study is to get a further insight of COX 2-thromboxane axis in podocyte injury.
Methods
In vitro study was performed with a high glucose medium of 30mmol/L to set up a podocyte injury model as previous described. Both the inhibitor and activator of the axis, small interfering RNA, ELISA, western blot and confocal were used to investigate the underlying mechanism of COX 2-thromboxane axis mediating podocyte injury.
Results
High glucose induced podocyte injury accompanied with increasing expression of COX 2 and excessive TXA2, indicating that the COX 2-thromboxane axis was activated. Small interfering RNA was used to silence the thromboxane/prostaglandin receptors (TP-r) or block the TP-r with inhibitor SQ29548 alleviated the injury. Furthermore, the stimulation of high glucose led to the over-activation of Rho/ROCK1 pathway, resulting in an increased phosphorylation of Drp1, a critical protein regulating mitochondrial fission. As expected, pretreatment of Y26432 could block the ROCK1 release protective effect when the cells were exposed to high glucose. What’s more, regulating of TXA2-TPr pathway with SQ29548, U46619 or small interfering RNA can affected the activity of Rho/ROCK pathway in podocytes stimulated with high glucose.
Conclusion
High glucose may activate the COX 2- thromboxane axis, leading to an activating activity of TP-r to induce the downstream effect of ROCK1 activated, resulting in excessive mitochondrial fission, and finally induced podocyte injury (Fig 1).
Funding
- Government Support - Non-U.S.