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Human mesangial cells resist glycoxidative stress through an antioxidant response
Mariapaola Nitti1, Anna Lisa Furfaro, Stefania Patriarca
1Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Abstract:
The generation of advanced glycation end-products (AGE), the interaction with their receptors, the generation of reactive oxygen species, and the modulation of intracellular redox equilibrium are believed to be the main factors causing alterations of mesangial cell physiology leading to diabetic nephropathy. Normal human primary mesangial cells were exposed to glycoxidative stress by culture in high glucose (HG) or treatment with AGE for up to 6 days. In both cases only a moderate generation of reactive oxygen species and production of HNE-protein adducts were induced while protein nitrotyrosination was not affected. Moreover, HG and AGE caused a significant antioxidant response, confirmed by the induction of heme oxygenase 1 and the consumption of vitamin E. Glutathione was decreased only by HG. Mesangial cell proliferation and viability were slightly affected by HG and AGE. Furthermore, both treatments failed to influence TGF-ß1 and MCP-1 secretion and to modulate RAGE and collagen IV expression. We believe that normal human mesangial cells can resist glycoxidative stress by the observed antioxidant response. These results support the concept that mesangial cells are only partly responsible for the onset and progression of diabetic nephropathy and that the role of other cell types, such as podocytes and endothelial cells, should be taken into consideration.
Insights
Normal human mesangial cells exhibit antioxidant defenses against advanced glycation end-products (AGE) and high glucose (HG), suggesting limited direct contribution to diabetic nephropathy progression.
Area of Science:
- Nephrology
- Cell Biology
- Metabolic Diseases
Background:
- Diabetic nephropathy involves advanced glycation end-products (AGE), receptor interactions, reactive oxygen species (ROS), and altered redox balance impacting mesangial cell function.
- Understanding mesangial cell response to glycoxidative stress is crucial for elucidating diabetic nephropathy pathogenesis.
Purpose of the Study:
- To investigate the physiological response of normal human mesangial cells to glycoxidative stress induced by high glucose (HG) and AGE.
- To assess the impact of HG and AGE on mesangial cell proliferation, viability, antioxidant mechanisms, and key signaling molecules.
Main Methods:
- Primary human mesangial cells were cultured in high glucose (HG) or treated with AGE for up to 6 days.
- Assessed reactive oxygen species (ROS) generation, HNE-protein adducts, protein nitrotyrosination, and antioxidant markers (heme oxygenase 1, vitamin E, glutathione).
- Evaluated mesangial cell proliferation, viability, TGF-ß1 and MCP-1 secretion, RAGE, and collagen IV expression.
Main Results:
- HG and AGE induced moderate ROS and HNE-protein adducts but did not affect protein nitrotyrosination.
- A significant antioxidant response was observed, including heme oxygenase 1 induction and vitamin E consumption; glutathione decreased with HG only.
- Mesangial cell proliferation and viability were only slightly affected, with no changes in TGF-ß1, MCP-1, RAGE, or collagen IV expression.
Conclusions:
- Normal human mesangial cells possess robust antioxidant mechanisms enabling resistance to glycoxidative stress.
- Mesangial cells may play a limited role in the early stages of diabetic nephropathy, highlighting the importance of other cell types like podocytes and endothelial cells.
