Abstract P193: Platelet-derived Growth Factor B: a Novel Determinant of Juxtaglomerular Cell Phenotypic Plasticity?

Abstract

Renin, a key component in the regulation of blood pressure in mammals, is produced by the rare and highly specialized juxtaglomerular (JG) cells of the kidney. JG cells may be derived from vascular smooth muscle cells (VSMC) and they can reversibly differentiate in response to changes in salt, blood pressure and treatment with anti-hypertensive medications. The biochemical mechanism responsible for this phenotypic plasticity is currently unknown. Ligands involved in VSMC differentiation include platelet-derived growth factor B (PDGF-B), secreted acidic protein rich in cysteine (SPARC), type-C natriuretic peptide (NPPC), follistatin related protein (FSTL1) and lactose-binding lectin 1 (LGALS1). To test for the role of these factors in JG cell plasticity we used (pro)renin-producing As4.1 cells derived from a mouse JG cell targeted tumor. As4.1 cells were incubated for 48 hours with conditioned medium derived from human embryonic kidney (HEK) 293 cells transfected with the mouse cDNA encoding these ligands, after which both medium and cell lysate were collected. Renin and prorenin were measured using the angiotensin I generation assay. Under control conditions, the medium contained predominantly (>95%) prorenin. In contrast, the cell lysate contained renin only, at levels corresponding to <1% of the total amount of renin+prorenin in the medium (i.e., 161±61 μg angiotensin I/ml.hr, mean±SEM). Among the tested ligands, only PDGF-B affected the medium prorenin and cellular renin levels, decreasing both in parallel by 68±5% and 53±10%, respectively. In addition, PDGF-B-exposed cells changed their morphology to display a more elongated, densely packed and aligned shape with no apparent alteration in their viability. In conclusion, our data suggest that PDGF-B might be one of the factors involved in JG cell phenotypic plasticity.