Abstract: TH-PO912
Glycolysis Inhibitors Suppress Renal Interstitial Fibrosis via Divergent Effects on Fibroblasts and Tubular Cells in Kidneys
Session Information
- Molecular Mechanisms of CKD - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Wei, Qingqing, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
- Su, Jennifer J., Augusta University, Martinez, Georgia, United States
- Dong, Zheng, Medical College of Georgia, Augusta, Georgia, United States
Background
Renal interstitial fibrosis is a common pathological feature of chronic kidney disease that may involve changes of the metabolism in kidney cells.
Methods
In this study, we first showed that blockade of glycolysis with two inhibitors [Dichloroacetate-DCA and shikonin] reduced renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO).
Results
Both inhibitors evidently suppressed the induction of fibronectin and collagen 1 in obstructed kidneys, while DCA also showed inhibitory effect on collagen IV and a-SMA. Histological examination also confirmed less collagen deposition in DCA treated kidneys. We also examined renal apoptosis by TUNEL assay and identified significant suppression of apoptosis after glycolysis blockage by both DCA and shikonin. We further examined their effects on fibrotic changes in cultured renal proximal tubular BUMPT cells and renal NRK-49F fibroblasts (cells). While glycolysis inhibitors reduced fibronectin and a-SMA production in NRK-49F cells, no obvious effect or even induction of fibronectin or a-SMA was detected in BUMPT cells during TGF-b1 or hypoxia stimulation.
Conclusion
Altogether, these results suggest that inhibition of glycolysis may reduce renal interstitial fibrosis by suppressing renal apoptosis and fibrotic alterations in fibroblasts.
Funding
- NIDDK Support