title: A functional (pro)renin receptor is expressed in human lymphocytes and monocytes.
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.
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Kaori
authors.initials: K
authors.lastname: Narumi
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Center for Interdisciplinary Research in Biology (CIRB), College de France, and CNRS UMR 7241 and INSERM U1050, Paris, France;
authors.forename: Takuo
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science, Sendai, Japan; emiko@med.tohoku.ac.jp.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sato
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Integrative Renal Replacement Therapy, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Kisu
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Mayuko
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Social Welfare, Faculty of Synthetic Welfare, Tohoku Fukushi University, Sendai, Japan; Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan;
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Totsune
authors.affiliation: Department of Hematology and Rheumatology, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.affiliation: Center for Interdisciplinary Research in Biology (CIRB), College de France, and CNRS UMR 7241 and INSERM U1050, Paris, France;
authors.forename: Genevieve
authors.initials: G
authors.lastname: Nguyen
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science, Sendai, Japan;
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Integrative Renal Replacement Therapy, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000328:Adult; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin; D020298:U937 Cells; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D055815:Young Adult; D000093342:Prorenin Receptor
chemical_list: D051546:Cyclooxygenase 2; D016207:Cytokines; D048049:Extracellular Signal-Regulated MAP Kinases; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C496540:PTGS2 protein, human
keywords: (pro)renin receptor; glomerulonephritis; human; lymphocytes; renin-angiotensin system