AVP infusion increases the expression of urea transporters and ER stress pathway genes in medullae of female mice with urinary concentrating defect

Abstract

Abnormal proliferation in collecting duct cells plays a crucial role in polycystic kidney disease (PKD) and in lithium‐induced renal dysfunction. Females with PKD demonstrate lower proliferation rates than males, resulting in a less severe phenotype. We previously reported that vasopressin induced an increase in renal cell proliferation in male AQP1KO mice in addition to ER stress gene activation. In this study we infused AVP for 14 days into female AQP1KO mice. AVP induced a small but significant increase in urine osmolality (155 mosmol/kgH20 vs control). 14 days AVP infusion significantly increased the expression of UTA1 and UTA3 mRNA 2.97 ± 0.29 and 3.34 ± 0.57, respectively, vs control. AQP2 and AQP3 mRNA also increased 3.52 ± 0.28 and 2.59 ± 0.23, vs control. AVP infusion significantly increased the mRNA expression of early growth response gene Egr‐1 2.49 ± 0.49 and transcription factors ATF3 and ATF4 mRNA; 4.91 ± 0.70, and 3.36 ± 0.25, vs control. AVP infusion significantly increased the expression of ER stress factor GADD153 mRNA 2.53 ± 0.41 vs control. AVP did not increase the mRNA expression of PCNA in female kidneys; PCNA is a marker of proliferation. These data suggest that vasopressin regulation of urea transporters is intact in female AQP1KO mice. Further studies will determine if vasopressin induced proliferative pathways are blunted in female AQP1KO mice.Support: DK073611 (HLB)