Abstract

Aims: The renin-angiotensin system (RAS) has been implicated in renal fibrosis through activation of the type 1 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. Materials and 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 (rs) 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-b (TGF-b) (rs 0.59; p = 0.044), matrix metalloproteinase-1 (MMP-1) (rs 0.83; p = 0.001), tissue inhibitor of metalloproteinase-2 (TIMP-2) (rs 0.74; p = 0.001) and TIMP-3 (rs 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.

Author Details

Authors

• B.N. Becker
• L.M. Jacobson
• D.A. Hullett
• N.A. Radke
• T.D. Oberley
• P.C. Brazy
• A.D. Kirk

Departments

• ¹ Department of Medicine, Division of Nephrology,
• ² Department of Surgery, Division of Transplantation,
• ³ Department of Pathology and Laboratory Medicine, University of Wisconsin, Department of Veterans Affairs Hospital, Madison, WI, and
• ⁴ NIDDK-Navy Transplantation and Autoimmunity Branch, National Naval Medical Center, Bethesda, MD, USA

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