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High glucose modifies heparansulphate synthesis by mouse glomerular epithelial cells
S Morano1, L Guidobaldi, R Cipriani
1Department of Endocrinology, Clinica Medica 2, University La Sapienza, Rome, Italy. smorano@uniroma1.it
Diabetes/Metabolism Research and Reviews
|July 9, 1999
Summary
High glucose significantly reduces proteoglycan synthesis in glomerular epithelial cells, indicating its role in diabetic nephropathy. This study establishes a reliable in vitro model for investigating the disease mechanisms.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Proteoglycan metabolism is implicated in diabetic nephropathy pathogenesis.
- Understanding high glucose effects on proteoglycans is crucial for diabetic nephropathy research.
Purpose of the Study:
- To investigate the impact of high glucose on proteoglycan production in glomerular epithelial cells.
- To establish a reliable in vitro model for studying diabetic nephropathy.
Main Methods:
- Cultured mouse glomerular epithelial cells with high glucose (30 mmol), normal glucose (5 mmol), or mannitol (30 mmol).
- Assessed proteoglycan synthesis using 35SO4 labeling and analyzed molecular composition via Sepharose CL6B and DEAE-Sephacel chromatography.
Main Results:
- High glucose (30 mmol) reduced total cell-layer proteoglycan synthesis by 56% and medium-associated synthesis by 25%.
- Specific heparan sulfate proteoglycan species (I and II) and glycosaminoglycan synthesis decreased significantly (81-91%) under high glucose conditions.
- Mannitol exposure showed less pronounced effects, suggesting high glucose, not just osmotic pressure, impacts proteoglycan metabolism.
Conclusions:
- Glomerular epithelial cells are key players in proteoglycan synthesis.
- High glucose alters the quantity and types of proteoglycans produced, with osmotic effects being secondary.
- The studied glomerular epithelial cell clone serves as a valid in vitro model for diabetic nephropathy research.