Renal transplantation modulates expression and function of receptors and transporters of rat proximal tubules.
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+-HCO(3)(-)-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.
Velic
Ana
A
Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Universitätsklinikum Münster, Domagkstrasse 3a, D-48149 Münster, Germany.
Hirsch
Jochen R
JR
Bartel
Jasmin
J
Thomas
Regina
R
Schröter
Rita
R
Stegemann
Heike
H
Edemir
Bayram
B
August
Christian
C
Schlatter
Eberhard
E
Gabriëls
Gert
G
D000818:Animals; D006863:Hydrogen-Ion Concentration; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012964:Sodium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051297:Sodium-Glucose Transporter 2; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C000613385:SLC9A3 protein, human; C422004:Slc4a4 protein, rat; C490300:Slc5a2 protein, rat; C000613387:Slc9a3 protein, rat; D027982:Sodium-Bicarbonate Symporters; D051297:Sodium-Glucose Transporter 2; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D012964:Sodium