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J Am Soc Nephrol 15:967-977, 2004
© 2004 American Society of Nephrology

BASIC SCIENCE

Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Ana Velic*, Jochen R. Hirsch*, Jasmin Bartel*, Regina Thomas*, Rita Schröter*, Heike Stegemann*, Bayram Edemir*, Christian August{dagger}, Eberhard Schlatter* and Gert Gabriëls*

*Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, and {dagger}Gerhard-Domagk-Institut für Pathologie, Universitätsklinikum Münster, Münster, Germany.

Correspondence to Prof. Dr. Eberhard Schlatter, Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstra{beta}e 3a, D-48149 Münster, Germany. Phone: 49-251-83-56991; Fax: 49-251-83-56973; E-mail: eberhard.schlatter{at}uni-muenster.de

ABSTRACT. Kidney transplantation often leads to disturbances of solute and volume maintenance in humans. To investigate underlying mechanisms, expression and function of renal transporters and receptors of the proximal tubule (PT) were analyzed in an acute rejection model of rat kidney transplantation. Semiquantitative RT-PCR and Western blot, histology, immunohistochemistry, and microfluorometry were performed on whole kidneys and isolated PT. With acute rejection, Na+/H+-exchanger type-3 (NHE-3) was markedly downregulated. Na+-HCO3--cotransporter (NBC-1) and Na+-glucose transporter type-2 (SGLT2) were upregulated after transplantation. Expressions of Na+/H+-exchanger type-1 (NHE-1), Na+/K+-ATPase (NKA), angiotensin II (AngII) receptor (AT-1), or natriuretic peptide receptor (GC-A) were unaltered. Microfluorometric analyses of intracellular pH, Na+, and Ca2+ demonstrated a decrease in NHE-3 function and AngII-mediated stimulation of NHE-3. AngII-mediated inhibition of NHE-1 and function of all other transporters tested remained unaltered. Function of AT-1 and GC-A were unaffected. Reduced expression of NHE-3 was also confirmed by semiquantitative immunohistochemistry. These findings suggest that expression and function of transmembrane proteins involved in Na+-transport after transplantation and rejection is specifically modulated. The local renin-angiotensin-system is apparently not altered. Downregulation of NHE-3 may be a protective mechanism occurring in the graft.




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B. Edemir, S. Reuter, R. Borgulya, R. Schroter, U. Neugebauer, G. Gabriels, and E. Schlatter
Acute Rejection Modulates Gene Expression in the Collecting Duct
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 538 - 546.
[Abstract] [Full Text] [PDF]


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