A functional (pro)renin receptor is expressed in human lymphocytes and monocytes

Kaori Narumi, Takuo Hirose, Emiko Sato, Takefumi Mori, Kiyomi Kisu, Mayuko Ishikawa, Kazuhito Totsune, Tomonori Ishii, Atsuhiro Ichihara, Genevieve Nguyen, Hiroshi Sato, Sadayoshi Ito

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The renin-angiotensin system (RAS) is involved in inflammation. The signaling via the ANG II type 1 receptor in human lymphocytes and monocytes, which play key roles in pathophysiology of glomerulonephritis (GN), can enhance inflammation. However, the role of the (pro)renin receptor [(P)RR], a component of the RAS, in inflammatory reactions is unknown. We assessed whether (P)RR is expressed in human lymphocytes and monocytes by RT-PCR, Western blotting, flow cytometry, and immunohistochemistry, and whether (P)RR functions in inflammation. (P)RR mRNA and protein were expressed in human peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis revealed high expression of (P)RR on monocytes. (P)RR was present on PBMCs, infiltrating lymphocytes, and macrophages around glomeruli with a crescent in anti-neutrophil cytoplasmic antibody (ANCA)-associated GN. Renin stimulation of PBMCs from healthy subjects in the presence of the ANG II type 1 receptor and ANG II type 2 receptor blockers induced ERK1/2 phosphorylation and release of IL-6 and expression of cyclooxygenase-2 (COX-2). The increases in cytokine release and COX-2 expression were inhibited in the presence of an ERK1/2 inhibitor. (P)RR knockdown by small interfering RNA in U937 cells, a human leukemic monocyte lymphoma cell line, significantly decreased ERK1/2 phosphorylation after renin stimulation. Thus (P)RR expressed in human inflammatory cells might contribute to inflammation in ANCA-associated GN.

Original languageEnglish
Pages (from-to)F487-F499
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number5
DOIs
Publication statusPublished - 2015 Jan 1

Keywords

  • (pro)renin receptor
  • Glomerulonephritis
  • Human
  • Lymphocytes
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Physiology
  • Urology

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