Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats

Y. Kaneshiro, A. Ichihara, T. Takemitsu, M. Sakoda, F. Suzuki, T. Nakagawa, M. Hayashi, T. Inagami

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Increased macula densa cyclooxygenase-2 (COX-2) is observed in diabetic rats and may contribute to hyperfiltration states. However, the signals mediating increased COX-2 expression in diabetic rats remain undetermined. We recently found that non-proteolytic activation of prorenin by site-specific binding proteins, such as prorenin receptor, plays a pivotal role in the development of diabetic nephropathy. The present study was designed to determine the contribution of prorenin receptor to renal cortical COX-2 expression. The COX-2 mRNA and protein levels of six 4-week-old male wild-type rats and six human prorenin receptor gene-transgenic (hProRenRcTg) rats were measured by real-time polymerase chain reaction methods, Western blotting, and immunohistochemistry, and compared. There were no differences between the two groups in arterial pressure measured by telemetry, urinary sodium excretion, or renal levels of rat prorenin receptor mRNA. The renal cortical COX-2 mRNA levels of the hProRenRcTg rats were significantly higher than those of the wild-type rats, and the renal cortical COX-2 protein levels were also higher in hProRenRcTg rats than in the wild-type rats. Immunohistochemical analysis revealed that COX-2 immunostaining was predominantly present in the macula densa cells, and significantly more COX-2-positive cells were present in the hProRenRcTg rats than in the wild-type rats. In addition, COX-2 inhibition with NS398 significantly decreased renal cortical blood flow in the hProRenRcTg rats but not in the wild-type rats. These results strongly suggest that human prorenin receptor directly or indirectly contributes to the regulation of renal cortical COX-2 expression.

Original languageEnglish
Pages (from-to)641-646
Number of pages6
JournalKidney international
Volume70
Issue number4
DOIs
Publication statusPublished - 2006 Aug 28

Keywords

  • Cyclooxygenase
  • Kidney
  • Microcirculation
  • Renal circulation
  • Renin

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats'. Together they form a unique fingerprint.

  • Cite this

    Kaneshiro, Y., Ichihara, A., Takemitsu, T., Sakoda, M., Suzuki, F., Nakagawa, T., Hayashi, M., & Inagami, T. (2006). Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats. Kidney international, 70(4), 641-646. https://doi.org/10.1038/sj.ki.5001627