Renin is a proteolytic enzyme released by the kidneys in response to a decrease in blood pressure or extracellular volume. The lineage identity, origin and possible turnover of renin-producing cells remains poorly understood. Recent reports suggest that renin-producing cells are precursors for multiple cell types in the kidney (1). We hypothesized that renin cells are related to pericytes, progenitor cells embedded in the microvascular wall (2). Since renal diseases are often associated with microvascular complications, studies of renal pericytes may identify a new potential target for therapeutic treatment of kidney disease. We have shown that during normal human development pericyte surface markers CD146 and NG2 label multiple kidney cells including interstitial capillaries, afferent arterioles, mesangial cells. We demonstrated that renin producing cells co-express pericyte markers in the juxtaglomerular region and along renal arterioles between 8-20 weeks of gestation. For the first time we have obtained primary cultures of renal pericytes from the developing human kidney. CD146+CD34-CD45-CD56- pericyte populations were isolated from the foetal human kidney via fluorescence-activated cell sorting (FACS). Cells maintained the selected phenotype through culture; they remained positive for pericyte markers and negative for haematopoietic and endothelial cell markers. Primary cultures of foetal renal pericytes showed tri-lineage mesodermal differentiation. Renin expression was induced by cAMP pathway stimulation (10 µm forskolin and 100 µm 3-isobutyl-1-methylxanthine [IBMX] 24h treatment) on the gene and protein level. In conclusion, a subset of pericytes co-express renin suggesting that renin cells have a perivascular origin. Renal pericytes are a widespread and abundant population in the human foetal kidney that can be isolated and propagated in vitro. Primary cultures of renal pericytes can be a model for renin cell recruitment. Future studies will investigate the mechanism through which pericytes switch into renin-producing cells and possible ways of manipulating the renin-angiotensin system by targeting pericytes.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCA378
Poster Communications: Pericytes derived from the human foetal kidney are progenitors for renin-producing cells
A. Stefanska1, J. Mullins1, B. Péault1,2
1. University/BHF Centre for Cardiovascular Science, Edinburgh, United Kingdom. 2. MRC Centre for Regenerative Medicine, Edinburgh, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.