Type 2 angiotensin II receptor expression in human renal allografts: an association with chronic allograft nephropathy.
OBJECTIVE
The renin-angiotensin system (RAS) has been implicated in renal fibrosis through activation of the type I angiotensin II (Ang II) receptor (AT1R). Whether the other predominant Ang II receptor, the type 2 Ang II receptor (AT2R), has a fibrotic or sparing role in adult human renal tissue is unknown.


METHODS
We used the reverse-transcription polymerase chain reaction (RT-PCR) to assess intragraft AT2R mRNA expression in biopsy samples from 23 renal transplant recipients. Potential correlations between intragraft AT2R mRNA. matrix-modulating genes and histologic evidence of chronic rejection were assessed.


RESULTS
AT2R mRNA was confirmed by sequence analysis of the RT-PCR product. AT2R mRNA expression directly correlated with angiotensinogen (Spearman correlation coefficient (r(s)) 0.72; p = 0.0011) mRNA expression, and interestingly, AT2R mRNA inversely correlated with inflammatory gene expression in the biopsy samples. However, AT2R mRNA directly correlated with transforming growth factor-beta (TGF-beta) (r(s) 0.59: p = 0.044), matrix metalloproteinase-1 (MMP-1) (r(s) 0.83; p = 0.001), tissue inhibitor of metalloproteinase-2 (TIMP-2) (r(s) 0.74; p = 0.001) and TIMP-3 (r(s) 0.80; p = 0.001) mRNA expression. Moreover, AT2R mRNA and protein expression was significantly greater in the patients with biopsy-proven chronic allograft nephropathy (n = 9; p = 0.045 vs. no chronic allograft nephropathy and donor biopsy samples for mRNA analyses).


CONCLUSIONS
These data demonstrate that AT2R mRNA is expressed in adult human renal tissue in the setting of renal transplantation. Its apparent association with matrix-modulating genes raises the hypothesis that AT2R mRNA expression may be linked with extracellular matrix regulation in the setting of chronic allograft nephropathy.
Becker
B N
BN
Department of Medicine, University of Wisconsin, Department of Veterans Affairs Hospital, Madison 53705, USA. bnb@medicine.wisc.edu
Jacobson
L M
LM
Hullett
D A
DA
Radke
N A
NA
Oberley
T D
TD
Brazy
P C
PC
Kirk
A D
AD
D000328:Adult; D001706:Biopsy; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis* / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D008666:Metalloendopeptidases