Maternal diabetes reduced megalin and cubilin levels in the fetal kidney

LAUTARO RECCHIA, CINTIA GATTI, MARÍA LAURA LEONARDI, ALICIA JAWERBAUM, ROMINA HIGA.

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Background: Maternal diabetes causes an altered development of different fetal organs, including the kidney, related to the programming of diseases in the offspring. The multiligand endocytic receptors Megalin and Cubilin are key receptors in the process of renal reabsorption, their expression can be modulated by the nuclear receptor PPARα. Megalin is a functional receptor for matrix metalloproteinase 9 (MMP9), mediating its endocytosis and catabolism. MMP9 is a proteolytic enzyme involved in morphogenesis, but also in pathological processes when overproduced. Aim: To evaluate PPARα mRNA levels and protein expression and localization of Megalin, Cubilin and MMP9 in the fetal kidney of control and diabetic rats on day 21 of gestation.Methods: Pregestational diabetic rats were obtained by neonatal administration of streptozotocin (90 mg/kg sc) and control rats were injected with vehicle. Both groups were mated with healthy males and fetal kidneys were obtained on day 21 of gestation to evaluate PPARα mRNA levels (RT-PCR) and megalin, cubilin and MMP9 (IHQ). Results: A decreased fetal kidney/fetal weight was found in the diabetic group (-30%,p