Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways.

Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-кB signaling pathways. Am J Physiol Renal Physiol. 2016 Feb 10;:ajprenal.00350.2015 Authors: Zhuo JL, Kobori H, Li XC, Sato R, Katsurada A, Navar LG Abstract Long-term angiotensin II (ANG II) infusion significantly increases ANG II levels in the kidney through two major mechanisms; AT1 receptor-mediated augmentation of angiotensinogen (AGT) expression and uptake of circulating ANG II by the proximal tubules. However, it is not known whether intracellular ANG II stimulates AGT expression in the proximal tubule. In the present study, we overexpressed an intracellular cyan fluorescent ANG II fusion protein (Ad-sglt2-ECFP/ANG II) selectively in the proximal tubule of rats and mice using the sodium and glucose co-transporter 2 (sglt2) promoter. AGT mRNA and protein expression in the renal cortex and 24 h urinary AGT excretion were determined 4 weeks following overexpression of ECFP/ANG II in the proximal tubule. Systolic blood pressure was significantly increased with a small antinatriuretic effect in rats and mice with proximal tubule-selective expression of ECFP/ANG II (p<0.01). AGT mRNA and protein expression in the cortex were increased by >1.5 fold and 61 ± 16% (p<0.05), whereas urinary AGT excretion was increased from 48.7 ± 5.7 (n=13) to 102 ± 13.5 (n=13) ng/24 h (p<0.05). However, plasma AGT, PRA, and ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research