Hyperglycemic levels in early stage of diabetic nephropathy affect differentially renal expression of claudins-2 and -5 by oxidative stress

Autor: Rafael Rodríguez-Muñoz, Alicia Sánchez-Mendoza, Luz Graciela Cervantes-Pérez, Maria del Carmen Namorado-Tónix, Lorena Rosas-Martínez, Fanis Missirlis, Leonardo Del Valle-Mondragón, José Luis Reyes-Sánchez
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
endocrine system diseases
Renal function
Kidney
urologic and male genital diseases
medicine.disease_cause
030226 pharmacology & pharmacy
Streptozocin
General Biochemistry
Genetics and Molecular Biology
Diabetes Mellitus
Experimental
Diabetic nephropathy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Sodium-Glucose Transporter 2
Diabetes mellitus
Internal medicine
Animals
Medicine
Claudin-2
Diabetic Nephropathies
Claudin-5
Rats
Wistar
General Pharmacology
Toxicology and Pharmaceutics
Claudin
Proteinuria
business.industry
Reabsorption
General Medicine
medicine.disease
Malondialdehyde
Oxidative Stress
Diabetes Mellitus
Type 1
030104 developmental biology
Endocrinology
Diabetes Mellitus
Type 2
Matrix Metalloproteinase 9
chemistry
Hyperglycemia
Matrix Metalloproteinase 2
medicine.symptom
business
Oxidative stress
Zdroj: Life Sciences. 268:119003
ISSN: 0024-3205
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: