Relationship between intracellular signaling of the (Pro)renin receptor and the pathogenesis of preeclampsia

Shoko Tamada, Takashi Mitsui, Akiko Ohira, Kazumasa Tani, Jota Maki, Takeshi Eguchi, Eriko Eto, Kei Hayata, Hisashi Masuyama

Research output: Contribution to journalArticle


An association between preeclampsia and (pro)renin was recently reported. Intracellular signaling of the (pro) renin receptor [(P)RR] increases the expressions of TGF-β and PAI-1. In this study we sought to clarify the involvement of (pro)renin in the pathogenesis of preeclampsia via the intracellular signaling of (P)RR on preeclampsia placentas. Activated (pro)renin plasma concentrations were compared between pregnant women with (n=15) and without (n=28) preeclampsia. The placentas were immunohistochemically evaluated with anti-HIF-1α and anti-(P)RR antibodies. HTR-8/SVneo cells were cultured under hypoxic conditions and treated with human recombinant (pro)renin. The mRNA expressions of HIF-1α, (P)RR, PAI-1, TGF-β, and ET-1 were also examined by real-time RCR. The activated (pro)renin plasma concentration was significantly higher in the third vs. the second trimester in the preeclampsia patients. HIF-1α and (P)RR expressions were significantly increased in the preeclampsia placentas. The mRNA expressions of PAI-1, TGF-β, and ET-1 were significantly increased in the experiments using recombinant (pro)renin vs. hypoxic conditions. (P)RR expression in preeclampsia placentas is increased by persistent hypoxia through the second and third trimesters, and PAI-1, TGF-β, and ET-1 production is increased via (P)RR. Our results suggest that ET-1 production via the intracellular signaling of (P)RR is important in the pathogenesis of preeclampsia.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalActa medica Okayama
Issue number5
Publication statusPublished - Jan 1 2019



  • (pro)renin
  • (pro)renin receptor
  • Endothelin-1
  • HTR-8/SVneo
  • Preeclampsia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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