Abstract: FR-PO202
Hyperoside Inhibits Podocyte Epithelial-Mesenchymal Transition in Diabetic Kidney Disease via Regulating Insulin Resistance-Related Signaling Pathways, Compared with Rosiglitazone
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
- Wu, Wei, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Liu, Yinglu, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
- Wan, Yigang, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
Group or Team Name
- Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
Background
Hyperoside (HYP), a bioactive component of Abelmoschus manihot, has been widely applied to clinical therapy in the diabetic kidney disease (DKD) patients. However, it remains elusive whether HYP can alleviate podocyte damage in DKD. The disordered activation of insulin resistance (IR)-related signaling pathways in the kidney induces podocyte epithelial-mesenchymal transition (EMT), further resulting in podocyte injury in DKD. Therefore, this study aimed to clarify the therapeutic effects of HYP on podocyte EMT in DKD and its underlying mechanisms, compare to rosiglitazone (ROS).
Methods
All rats were randomly divided into 4 groups, the Sham, the Vehicle, the HYP and the ROS groups. The appropriate doses of HYP, ROS and distilled water were administrated with oral for 6 weeks after the induction of DKD by high fat feed, mononephrectomy and streptozotocin intraperitoneal injection, respectively.The changes in podocyte EMT-related parameters in urine and blood were analyzed. The kidneys were isolated for histomorphometry, immunohistochemistry and Western blotting (WB) at sacrifice. In vitro, murine potocytes were used to investigate the inhibitory actions of HYP on IR-associated signaling pathways by WB, compared to ROS.
Results
For the DKD model rats, HYP and ROS ameliorated IR, glomerulosclerosis (GS), glomerular basement membrane (GBM) thickening and foot process effacement, and the effects of HYP on GS and GBM thickening were superior to ROS; HYP and ROS improved the protein expressions of podocyte EMT markers in the kidney including nephrin, P-Cadherin, collagen-1 and desmin, and the effects of HYP were similar to ROS; In addition, HYP and ROS regulated the protein expressions of the key signaling molecules in IR-related signaling pathways including TGF-β1/Smad3, GLUT4 and Erk1/2 pathways, respectively, and the targets of HYP were similar to ROS. In vitro, the disordered phosphorylation of TGF-β1/Smad3, GLUT4 and Erk1/2 pathways in podocyte induced by high-glucose was reversed by the treatment of HYP or ROS.
Conclusion
We expounded that HYP inhibits podocyte EMT in DKD via regulating IR-regulated signaling pathways including TGF-β1/Smad3, GLUT4 and Erk1/2 pathways in the kidney, respectively. Overall, this study provided the first evidence that HYP directly contributes to the prevention of podocyte lesion in DKD.
Funding
- Government Support - Non-U.S.