| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark; Institute of Anatomy, University of Aarhus, Aarhus C, Denmark
2 Department of Physiology, College of Medicine, University of Arizona, Tucson, USA
3 The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu, Korea, Republic of
4 The Water and Salt Research Center, University of Aarhus, Aarhus C, Denmark; Institute of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark
* To whom correspondence should be addressed. E-mail: sn{at}ana.au.dk.
Lithium treatment is associated with development of nephrogenic diabetes insipidus (NDI), caused in
part by downregulation of collecting duct AQP2 and AQP3 expression. In the present study we
carried out cDNA microarray screening of gene expression in the inner medulla (IM) of
lithium-treated and control rats, and selected genes were then investigated at the protein level by
immunoblotting and/or immunohistochemistry. The following genes exhibited significantly altered
transcription and mRNA expression levels, and these were compatible with the changes in protein
expression. The 11-beta-hydroxysteroid dehydrogenase type 2 (11-
-HSD2) protein expression in
the IM was markedly increased (198 ± 25 % of controls, n=6) and immunocytochemistry
demonstrated an increased labeling of IMCD principal cells. This indicated altered renal
mineralocorticoid/glucocorticoid responses in lithium-treated rats. The inhibitor of cyclin-dependent
kinases p27 (KIP) protein expression was significantly decreased or undetectable in the IMCD cells,
pointing to increased cellular proliferation and remodeling. Heat shock protein 27 (Hsp27) protein
expression was decreased in the IM (64 ± 6 % of controls, n=6), likely to be associated with the
decreased medullary osmolality in lithium-treated rats. Consistent with this, lens aldose reductase
(AR) protein expression was markedly decreased in the IM (16 ± 2 % of controls, n=6) and
immunocytochemistry revealed decreased expression in the thin limb cells in the middle and terminal
parts of the IM. Ezrin protein expression was upregulated in the IM (158 ± 16 % of controls, n=6),
where it was predominantly expressed in the apical and cytoplasmic domain of the IMCD cells.
Increased ezrin expression indicated remodeling of actin cytoskeleton and/or altered regulation of
IMCD transporters. In conclusion, the present study demonstrates changes in gene expression not
only in the collecting duct but also in the thin limb of the loop of Henle in inner medulla, and several
of these genes are linked to altered sodium and water reabsorption, cell cycling, and changes of
interstitial osmolality.
This article has been cited by other articles:
|
|
 |
|
  N. Schliebe, R. Strotmann, K. Busse, D. Mitschke, H. Biebermann, L. Schomburg, J. Kohrle, J. Bar, H. Rompler, J. Wess, et al. V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1177 - F1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Bedford, S. Weggery, G. Ellis, F. J. McDonald, P. R. Joyce, J. P. Leader, and R. J. Walker Lithium-induced Nephrogenic Diabetes Insipidus: Renal Effects of Amiloride Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1324 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Bedford, J. P. Leader, R. Jing, L. J. Walker, J. D. Klein, J. M. Sands, and R. J. Walker Amiloride restores renal medullary osmolytes in lithium-induced nephrogenic diabetes insipidus Am J Physiol Renal Physiol, April 1, 2008; 294(4): F812 - F820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Frohlich, D. Aggarwal, J. D. Klein, K. J. Kent, Y. Yang, R. B. Gunn, and J. M. Sands Stimulation of UT-A1-mediated transepithelial urea flux in MDCK cells by lithium Am J Physiol Renal Physiol, March 1, 2008; 294(3): F518 - F524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Uawithya, T. Pisitkun, B. E. Ruttenberg, and M. A. Knepper Transcriptional profiling of native inner medullary collecting duct cells from rat kidney Physiol Genomics, January 17, 2008; 32(2): 229 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Cai, M. R. McReynolds, M. Keck, K. A. Greer, J. B. Hoying, and H. L. Brooks Vasopressin receptor subtype 2 activation increases cell proliferation in the renal medulla of AQP1 null mice Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1858 - F1864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Catania, G. Chen, and A. R. Parrish Role of matrix metalloproteinases in renal pathophysiologies Am J Physiol Renal Physiol, March 1, 2007; 292(3): F905 - F911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol, August 1, 2006; 291(2): F257 - F270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yang, D. Zhao, L. Qian, and A. S. Verkman Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion Am J Physiol Renal Physiol, August 1, 2006; 291(2): F465 - F472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Christensen, Y.-H. Kim, T.-H. Kwon, and S. Nielsen Lithium treatment induces a marked proliferation of primarily principal cells in rat kidney inner medullary collecting duct Am J Physiol Renal Physiol, July 1, 2006; 291(1): F39 - F48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Fujiwara and D. G. Bichet Molecular Biology of Hereditary Diabetes Insipidus J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2836 - 2846. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
