Expression of (Pro)renin receptor during rapamycin-induced erythropoiesis in K562 erythroleukemia cells and its possible dual actions on erythropoiesis

Kiriko Kaneko, Koji Ohba, Takuo Hirose, Kazuhito Totsune, Kazumichi Furuyama, Kazuhiro Takahashi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is expressed in erythroblastic cells. (P)RR has multiple biological actions: prorenin activation, stimulation of the intracellular signaling including extracellular signal-regulated kinases, and functional complex formation with vacuolar H+-ATPase (v-ATPase). However, the functional implication of (P)RR in erythroblast cells has not been clarified. The aim of the present study was to clarify changes of (P)RR expression during erythropoiesis and a role of (P) RR in the heme synthesis. (P)RR expression was studied during rapamycin-induced erythropoiesis in a human erythroleukemia cell line, K562. Treatment with rapamycin (100 nM) for 48 hours significantly increased %number of hemoglobin-producing cells, γ-globin mRNA levels, erythroid specific 5-aminolevulinate synthase (ALAS2) mRNA levels, and heme content in K562 cells. Both (P)RR protein and mRNA levels increased about 1.4-fold during rapamycin-induced erythropoiesis. Suppression of (P) RR expression by (P)RR-specific small interference RNA increased ALAS2 mRNA levels about 1.6-fold in K562 cells, compared to control using scramble RNA, suggesting that (P)RR may down-regulate ALAS2 expression. By contrast, treatment with bafilomycin A1, an inhibitor of v-ATPase, decreased greatly % number of hemoglobin-producing cells and heme content in K562 cells, indicating that the v-ATPase function is essential for hemoglobinization and erythropoiesis. Treatment with bafilomycin A1 increased (P) RR protein and mRNA levels. In conclusion, we propose that (P)RR has dual actions on erythropoiesis: the promotion of erythropoiesis via v-ATPase function and the down-regulation of ALAS2 mRNA expression. Thus, (P)RR may contribute to the homeostatic control of erythropoiesis.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalTohoku Journal of Experimental Medicine
Volume241
Issue number1
DOIs
Publication statusPublished - 2017 Jan

Keywords

  • (pro)renin receptor
  • Erythropoiesis
  • Heme
  • Prorenin
  • Rapamycin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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