Vasopressin increases ATF3 mRNA expression in mouse renal inner medulla

In renal inner medulla (IM) the concentration of urea is high and variable depending on the concentrating mechanism. During water restriction (WR), the level of vasopressin increases, followed by further increase of urea concentration in IM. Expression of activating transcription factor 3 (ATF3) is increased by high urea in vitro. To determine whether ATF3 is regulated by high urea in vivo, we water restricted mice for 48 hours and found that ATF3 mRNA increased by 3.81 ± 0.24 fold vs. control 1.00 ± 0.06 (p≤0.05). 7 day infusion of AVP increased ATF3 mRNA by 1.69 ± 019 fold vs. control 1.00 ± 0.15 (p≤0.05). However, 7 day infusion of dDAVP, an agonist of type 2 vasopressin receptor, did not cause significant change in the expression of ATF3 mRNA. ATF3 is an important component in the pathway of endoplasmic reticulum (ER) stress. We previously found that GCN2, a kinase in ER stress pathway, was involved in high urea associated increase of ATF3 in vitro. However, there was no difference in the basal level of ATF3 mRNA between GCN2 null and wild type mice. As in wild type mice, 48 hours of WR increased ATF3 mRNA in IM of GCN2 null mice by 4.14 ± 0.09 fold vs. control GCN2 null mice 1.00 ± 0.06 (p≤0.05). Knocking down GRP78, an important ER chaperone, in mIMCD3 cells did not affect high urea induced increase of ATF3 protein. We concluded that deficiency of ER stress genes does not affect vasopressin induced increase of ATF3 in renal IM.