Abstract: FR-PO309
Investigating the Therapeutic Potential of Mannose in Diabetic Nephropathy: Targeting Epithelial-Mesenchymal Transition
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Ma, Sharui, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
- Song, Liumei, Xi'an Jiaotong University, Xi'an, Shaanxi, China
- Liu, Xiangchun, The Second Hospital of Shandong University, Jinan, Shandong, China
Background
Diabetic nephropathy progression often involves epithelial-mesenchymal transition (EMT) of proximal tubular epithelial cells, driven in part by the activation of transforming growth factor-beta (TGF-β) signaling in response to high glucose levels. Mannose, a hexose sugar, has shown promise in mitigating type 2 diabetes progression by suppressing TGF-β activity and enhancing regulatory T (Treg) cell function.
Methods
Human renal proximal tubular epithelial cells (HRPTECs) were cultured and subjected to control conditions, high glucose exposure, or high glucose combined with mannose treatment. Cell migration was assessed using wound scratch assays, and the expression of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin) was analyzed via Western blotting. Further experiments investigated the regulatory effect of mannose on TGF-β through Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and co-immunoprecipitation assays. Rescue experiments involved the overexpression of TGF-β followed by assessment of EMT reversal.
Results
High glucose exposure significantly promoted EMT in HRPTECs, whereas mannose treatment effectively reversed this progression. Mannose also attenuated the upregulation of EMT-related proteins induced by high glucose. Mechanistically, mannose was found to reduce TGF-β protein levels through increased ubiquitination and subsequent degradation, without affecting mRNA levels. Notably, overexpression of TGF-β counteracted the mesenchymal-epithelial transition (MET) induced by mannose, confirming the inhibitory effect of mannose on EMT via TGF-β regulation.
Conclusion
Our findings demonstrate that mannose inhibits high-glucose-induced EMT in HRPTECs by promoting the degradation of TGF-β. This suggests the therapeutic potential of mannose, a simple sugar, in the treatment of diabetic nephropathy.
Funding
- Government Support – Non-U.S.