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

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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

Fingerprint

Transgenic Rats
Cyclooxygenase 2
Kidney
Genes
Messenger RNA
human ATP6AP2 protein
Telemetry
Renal Circulation
Diabetic Nephropathies
Renin
Real-Time Polymerase Chain Reaction
Carrier Proteins
Arterial Pressure
Proteins
Western Blotting
Sodium
Immunohistochemistry

Keywords

  • Cyclooxygenase
  • Kidney
  • Microcirculation
  • Renal circulation
  • Renin

ASJC Scopus subject areas

  • Nephrology

Cite this

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

Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats. / Kaneshiro, Y.; Ichihara, A.; Takemitsu, T.; Sakoda, M.; Suzuki, F.; Nakagawa, T.; Hayashi, M.; Inagami, T.

In: Kidney International, Vol. 70, No. 4, 28.08.2006, p. 641-646.

Research output: Contribution to journalArticle

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, vol. 70, no. 4, pp. 641-646. https://doi.org/10.1038/sj.ki.5001627
Kaneshiro, Y. ; Ichihara, A. ; Takemitsu, T. ; Sakoda, M. ; Suzuki, F. ; Nakagawa, T. ; Hayashi, M. ; Inagami, T. / Increased expression of cyclooxygenase-2 in the renal cortex of human prorenin receptor gene-transgenic rats. In: Kidney International. 2006 ; Vol. 70, No. 4. pp. 641-646.
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AU - Sakoda, M.

AU - Suzuki, F.

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AU - Hayashi, M.

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AB - 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.

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