RGD Reference Report - Downregulation of renal aquaporins in response to unilateral ureteral obstruction. - Rat Genome Database

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Downregulation of renal aquaporins in response to unilateral ureteral obstruction.

Authors: Li, C  Wang, W  Knepper, MA  Nielsen, S  Frokiaer, J 
Citation: Li C, etal., Am J Physiol Renal Physiol 2003 May;284(5):F1066-79.
RGD ID: 704407
Pubmed: PMID:12517734   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00090.2002   (Journal Full-text)

The expression of aquaporin-2 (AQP2) is decreased in rats with bilateral ureteral obstruction (BUO) and unilateral ureteral obstruction (UUO). Therefore, the expression of additional renal aquaporins (AQP1-4) and phosphorylated AQP2 (p-AQP2), known to play a role in urinary concentration, was examined in a Wistar rat model with 24 h of UUO. In obstructed kidneys, immunoblotting revealed a significant decrease in the expression of inner medullary AQP2 to 42 +/- 4, p-AQP2 to 23 +/- 5, AQP3 to 19 +/- 6, AQP4 to 11 +/- 5, and AQP1 to 64 +/- 8% of sham levels. AQP1 expression located in the proximal tubule decreased to 74 +/- 4% of sham levels (P < 0.05). Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2. In contralateral nonobstructed kidneys, immunoblotting also revealed significant reductions of AQP1 in the inner medulla, outer medulla, and cortex, whereas expression of AQP2, AQP3, AQP4, and p-AQP2 was unchanged. Furthermore, we collected the urine from both obstructed and nonobstructed kidneys for 2 h, respectively, after 24 h of UUO. Urine collection from obstructed kidneys during 2 h after release of UUO revealed a significant reduction in urine osmolality and solute-free water reabsorption (T(c)H(2)O). Moreover, an increase in urine production and T(c)H(2)O was observed in contralateral kidneys. To examine whether vasopressin-independent mechanisms are involved in AQP2 regulation, vasopressin-deficient Brattleboro (BB) rats with 24 h of UUO were examined. Immunoblotting revealed downregulation of AQP2, p-AQP2, AQP3, and AQP1 in obstructed kidneys and downregulation of p-AQP2 and AQP1 in nonobstructed kidneys. In conclusion, 1) UUO is associated with severe downregulation of AQP2, AQP3, AQP4, and AQP1; thus all of these AQPs may play important roles in the impaired urinary concentrating capacity in the obstructed kidney; 2) the reduced levels of AQP1 in the nonobstructed kidney may contribute to the compensatory increase in urine production; and 3) downregulation of AQPs in BB rats supports the view that vasopressin-independent pathways may be involved in AQP2 and AQP3 regulation in the obstructed kidney.

Objects referenced in this article
Gene AQP3 aquaporin 3 (Gill blood group) Homo sapiens
Gene Aqp1 aquaporin 1 Rattus norvegicus
Gene Aqp2 aquaporin 2 Rattus norvegicus
Gene Aqp3 aquaporin 3 (Gill blood group) Rattus norvegicus
Gene Aqp4 aquaporin 4 Rattus norvegicus

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