Paricalcitol modulates ace2 shedding and renal adam17 in nod diabetic mice beyond proteinuria.

PARICALCITOL MODULATES ACE2 SHEDDING AND RENAL ADAM17 IN NOD DIABETIC MICE BEYOND PROTEINURIA. Am J Physiol Renal Physiol. 2015 Dec 23;:ajprenal.00082.2015 Authors: Riera M, Anguiano L, Clotet S, Roca-Ho H, Rebull M, Pascual J, Soler MJ Abstract Circulating and renal ACE2 activity is increased in the NOD diabetic mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17 a metalloprotease implied in ACE2 shedding was assessed. Diabetic NOD females and non-diabetic controls were studied for 21 days after diabetes onset and divided into different treatment groups. Diabetic animals received vehicle; paricalcitol at 0.4μg kg-1 or 0.8μg kg-1; aliskiren; or the combination. Furthermore, we studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren significantly reduced circulating ACE2 activity in diabetic NOD mice without changes in urinary albumin excretion. Serum renin activity significantly decreased in aliskiren-receiving groups but no effect was found with paricalcitol. Renal content of ADAM17 significantly decreased in animals receiving high dose of paricalcitol. Renal and circulating oxidative stress was reduced in high-dose paricalcitol group as compared to non-treated diabetic mice. In culture, paricalcitol significant...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research