Glucocorticoid mediates the transcription of OAT-PG, a kidney-specific prostaglandin transporter

Ryo Hatano, Hiroki Mukouchi, Yosuke Matsumoto, Kotoku Kawaguchi, Itsuro Kazama, Yasuhiro Endo, Hiroaki Toyama, Yutaka Ejima, Shin Kurosawa, Yoshikatsu Kanai, Mitsunobu Matsubara, Shinji Asano

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

OAT-PG is a kidney-specific prostaglandin transporter and exclusively expressed at the basolateral membrane of proximal tubules in rodent kidneys. We previously reported that OAT-PG was dominantly expressed in the male kidney similar to the other SLC22 family proteins as organic anion transporter (OAT) 1 and OAT3. Recently, Wegner et al. revealed that a transcription factor, B-cell CLL/lymphoma 6 (BCL6), is associated with the male-dominant expressions of OAT1 and OAT3 in the rat kidney. Here, we performed the luciferase assay to investigate whether OAT-PG is also transcriptionally regulated by BCL6. However, the promoter activity of OAT-PG was not directly affected by BCL6 overexpression nor the testosterone treatment, suggesting that different regulatory mechanisms underlie the male-dominant transcriptional regulation of OAT-PG compared to those of OAT1 and OAT3. We newly found that adrenalectomy (Adx) of male rat caused a significant reduction of OAT-PG expression without any significant changes in the OAT1 and OAT3 expressions, and it was recovered by the dexamethasone administration. Furthermore, the renocortical PGE 2 concentration was markedly increased in Adx male rat, concomitant with the downregulation of OAT-PG, and it was reduced to the basal level by dexamethasone treatment. In the luciferase assay, dexamethasone stimulated OAT-PG promoter activity but not OAT1. The luciferase activity responsiveness to dexamethasone was significantly reduced by the deletion of glucocorticoid response elements in the OAT-PG promoter region. These results suggest that glucocorticoid plays an important role in the regulation of the renocortical PGE2 concentration by the transcriptional regulation of OAT-PG in the rat kidney.

Original languageEnglish
Pages (from-to)925-935
Number of pages11
JournalPflugers Archiv European Journal of Physiology
Volume466
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Adrenalectomy
  • Gender difference
  • Organic anion transporter
  • Prostaglandin
  • Transcriptional regulation

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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