Hyperglycemic levels in early stage of diabetic nephropathy affect differentially renal expression of claudins-2 and -5 by oxidative stress.
AIMS
This study attempts to elicit whether the level of hyperglycemia in an early stage of diabetic nephropathy changes the renal expression of claudins-2 and -5 and to determine the involvement of glucose-induced oxidative stress.


MAIN METHODS
Streptozotocin-induced type-1 and type-2 diabetic (DM1, DM2)-rat models were used. At 14-week old, the rats were placed in metabolic cages to evaluate proteinuria, creatinine clearance, and electrolyte excretion. Proximal tubules and glomeruli were isolated and analyzed by Western blot and immunofluorescence. Renal oxidative stress and metalloproteinase activities were evaluated.


KEY FINDINGS
We found that claudin-5 expression in glomeruli and claudin-2 expression in proximal tubules were significantly reduced in DM1 versus DM2 model, paralleling with higher proteinuria and loss of sodium and potassium reabsorption, increased malondialdehyde levels, but lower antioxidant capacity in both models. Enzymatic activity of MMP-2 and-9 was increased in both diabetic groups versus control being higher in DM1 than DM2, suggesting higher claudin's degradation.


SIGNIFICANCE
The level of hyperglycemia determines the time-dependent progression to diabetic nephropathy; hyperglycemia-induced oxidative stress parallels an increase in metalloproteinases (MMPs) activities consequently affecting the integrity of claudin-2 and -5 in glomerulus and proximal tubule. Our results suggest that chronic high-glycemia levels in early stages of diabetic nephropathy decrease expression of claudins-2 and -5, increase oxidative stress, and induce MMP-activity faster than chronic middle-glycemia levels.
['Rosas-Martínez|Lorena|L|', 'Rodríguez-Muñoz|Rafael|R|', 'Namorado-Tonix|María Del Carmen|MDC|', 'Missirlis|Fanis|F|', 'Del Valle-Mondragón|Leonardo|L|', 'Sánchez-Mendoza|Alicia|A|', 'Reyes-Sánchez|José L|JL|', 'Cervantes-Pérez|Luz Graciela|LG|']
D000818:Animals D062446:Claudin-2 D062507:Claudin-5 D003921:Diabetes Mellitus, Experimental D003922:Diabetes Mellitus, Type 1 D003924:Diabetes Mellitus, Type 2 D003928:Diabetic Nephropathies D006943:Hyperglycemia D007668:Kidney D008297:Male D020778:Matrix Metalloproteinase 2 D020780:Matrix Metalloproteinase 9 D018384:Oxidative Stress D017208:Rats, Wistar D051297:Sodium-Glucose Transporter 2 D013311:Streptozocin
Diabetic nephropathy Oxidative stress Metalloproteinases Claudins Diabetes mellitus Renal tight junctions