TY - JOUR
T1 - Changes of rat kidney AQP2 and Na,K-ATPase mRNA expression in lithium-induced nephrogenic diabetes insipidus
AU - Laursen, Ulla Helt
AU - Pihakaski-Maunsbach, Kaarina
AU - Kwon, Tae Hwan
AU - Jensen, Erik Østergaard
AU - Nielsen, Søren
AU - Maunsbach, Arvid B.
PY - 2004
Y1 - 2004
N2 - Background/Aim: In a rat model, lithium treatment is associated with polyuria and severe downregulation of aquaporin-2 (AQP2) protein in the inner medulla (IM) or in the whole kidney. However, it is not known (1) to what extent this downregulation occurs at the mRNA level; (2) whether the main sodium transporter of the nephron, Na,K-ATPase, is regulated in parallel at the mRNA level, and (3) whether lithium treatment induces zonal or segmental differences in AQP2 and Na,K-ATPase mRNA levels. Method: We examined the changes in mRNA expression levels for AQP2 and Na,K-ATPase in kidney cortex, inner stripe of the outer medulla (ISOM), and IM of rats treated with lithium orally using semiquantitative Northern blot analyses and in situ hybridization at the light and electron microscopic levels. Results: The AQP2 mRNA levels decreased significantly (p < 0.01) in lithium-treated rats to 37 ± 4% in the cortex, to 17 ± 4% in the ISOM, and to 23 ± 5% in the IM, while the Na,K-ATPase mRNA levels were not altered in the cortex, but were significantly (p < 0.05) altered in the ISOM (144 ± 15% after 10 days, but 68 ± 4% after 4 weeks) and in the IM (63 ± 8% after 10 days, but normalized after 4 weeks). In situ hybridization showed reduced levels of AQP2 mRNA in all zones of the kidney, but the Na,K-ATPase mRNA expressions were slightly decreased only in IM collecting ducts. At the ultrastructural level, principal cells in the IM collecting ducts showed slight hypertrophy, but no cell damage after 4 weeks of lithium treatment. The results demonstrate substantial downregulation of AQP2 at the mRNA level throughout the collecting duct in experimental lithium-induced nephrogenic dabetes insipidus and moderately decreased Na,K-ATPase mRNA levels in the ISOM and in the IM. Conclusion: The results suggest that decreased mRNA expressions of AQP2 and Na,K-ATPase contribute to the development of lithium-induced nephrogenic diabetes insipidus.
AB - Background/Aim: In a rat model, lithium treatment is associated with polyuria and severe downregulation of aquaporin-2 (AQP2) protein in the inner medulla (IM) or in the whole kidney. However, it is not known (1) to what extent this downregulation occurs at the mRNA level; (2) whether the main sodium transporter of the nephron, Na,K-ATPase, is regulated in parallel at the mRNA level, and (3) whether lithium treatment induces zonal or segmental differences in AQP2 and Na,K-ATPase mRNA levels. Method: We examined the changes in mRNA expression levels for AQP2 and Na,K-ATPase in kidney cortex, inner stripe of the outer medulla (ISOM), and IM of rats treated with lithium orally using semiquantitative Northern blot analyses and in situ hybridization at the light and electron microscopic levels. Results: The AQP2 mRNA levels decreased significantly (p < 0.01) in lithium-treated rats to 37 ± 4% in the cortex, to 17 ± 4% in the ISOM, and to 23 ± 5% in the IM, while the Na,K-ATPase mRNA levels were not altered in the cortex, but were significantly (p < 0.05) altered in the ISOM (144 ± 15% after 10 days, but 68 ± 4% after 4 weeks) and in the IM (63 ± 8% after 10 days, but normalized after 4 weeks). In situ hybridization showed reduced levels of AQP2 mRNA in all zones of the kidney, but the Na,K-ATPase mRNA expressions were slightly decreased only in IM collecting ducts. At the ultrastructural level, principal cells in the IM collecting ducts showed slight hypertrophy, but no cell damage after 4 weeks of lithium treatment. The results demonstrate substantial downregulation of AQP2 at the mRNA level throughout the collecting duct in experimental lithium-induced nephrogenic dabetes insipidus and moderately decreased Na,K-ATPase mRNA levels in the ISOM and in the IM. Conclusion: The results suggest that decreased mRNA expressions of AQP2 and Na,K-ATPase contribute to the development of lithium-induced nephrogenic diabetes insipidus.
KW - AQP2 mRNA
KW - In situ hybridization
KW - Na,K-ATPase mRNA
KW - Nephrogenic diabetes insipidus
KW - Northern blotting
KW - Sodium transport
KW - Urinary concentration mechanism
KW - Water transport
UR - http://www.scopus.com/inward/record.url?scp=2542570242&partnerID=8YFLogxK
U2 - 10.1159/000077593
DO - 10.1159/000077593
M3 - Article
C2 - 15153756
AN - SCOPUS:2542570242
SN - 1660-2129
VL - 97
SP - e1-e16
JO - Nephron - Experimental Nephrology
JF - Nephron - Experimental Nephrology
IS - 1
ER -
