Effects of adrenomedullin on the glomerular adrenomedullin system in a rat model of anti-thy1 glomerulonephritis.
BACKGROUND
Adrenomedullin (ADM) has antiproliferative effects on glomerular mesangial cells. The study was performed to determine changes in glomerular gene expression of the ADM system by ADM treatment in anti-Thy1 glomerulonephritis (GN).


METHODS
GN in rats was induced by injecting anti-Thy-1 antibody. To show the effect of ADM treatment, rats received ADM from day 3 to day 6 of GN. Supplemental rats were sacrificed on day 3, 7 and 14 of GN to show the expression pattern of adrenomedullin and its receptors. Glomeruli were prepared by sieving or laser-assisted microdissection. Expression of ADM, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMP) 1-3, CD34, Thy1 and nephrin was analyzed using real-time PCR.


RESULTS
During GN a reduction of CLR and RAMP 2 + 3 expressions was detected on days 3, 7 and 14, while RAMP 1 rose. ADM mRNA decreased on days 3 and 7. Thy1 expression as a surrogate of mesangial cell number was downregulated during GN. A significant reduction of CD34 expression, as a surrogate for endothelial cell number, was detected on day 7. A tendency towards reduction of nephrin gene expression, as a surrogate for number of podocytes, was seen. The administration of ADM during GN did not change the expression on Thy1, CD34 or nephrin. The results were similar for microdissected and sieved glomeruli. In ADM-treated GN animals ADM gene expression rose compared to untreated GN animals on day 6. These effects were detected both in sieved and microdissected glomeruli. ADM administration did not change the expression of the receptors.


CONCLUSIONS
The downregulation of adrenomedullin during GN at the gene level can be improved by ADM application.
Geissler
Bettina
B
Kinder- und Jugendklinik, Erlangen, Germany.
Plank
Christian
C
Hartner
Andrea
A
Amann
Kerstin
K
Struwe
Friedrich G
FG
Hilgers
Karl F
KF
Rascher
Wolfgang
W
Dötsch
Jörg
J
D053607:Adrenomedullin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000235:genetics; D058286:Calcitonin Receptor-Like Protein; D015536:Down-Regulation; D005921:Glomerulonephritis / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007518:Isoantibodies; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism
D018952:Antigens, CD34; D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D007518:Isoantibodies; D008565:Membrane Proteins; D058261:Receptor Activity-Modifying Proteins; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D043562:Receptors, G-Protein-Coupled; C081830:adrenomedullin receptor, rat; C035678:anti-Thy antibody; C113267:nephrin; D053607:Adrenomedullin