Journal
KIDNEY INTERNATIONAL
Volume 90, Issue 6, Pages 1251-1261Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2016.07.035
Keywords
CD146; mesenchymal stem cell; nephrogenesis; NG2; pericyte; renin; tissue RAS
Categories
Funding
- British Heart Foundation (BHF) Centre of Research Excellence (CoRE) award
- BHF
- British Heart Foundation [R42775]
- Medical Research Council
- MRC [G1000816, G0901697] Funding Source: UKRI
- Medical Research Council [G1000816, 1576883, G0901697] Funding Source: researchfish
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Pericytes, perivascular cells embedded in the microvascular wall, are crucial for vascular homeostasis. These cells also play diverse roles in tissue development and regeneration as multi-lineage progenitors, immunomodulatory cells and as sources of trophic factors. Here, we establish that pericytes are renin producing cells in the human kidney. Renin was localized by immunohistochemistry in CD146 and NG2 expressing pericytes, surrounding juxtaglomerular and afferent arterioles. Similar to pericytes from other organs, CD146(+)CD34(-)CD45(-)CD56(-) renal fetal pericytes, sorted by flow cytometry, exhibited tri-lineage mesodermal differentiation potential in vitro. Additionally, renin expression was triggered in cultured kidney pericytes by cyclic AMP as confirmed by immuno-electron microscopy, and secretion of enzymatically functional renin, capable of generating angiotensin I. Pericytes derived from second trimester human placenta also expressed renin in an inducible fashion although the renin activity was much lower than in renal pericytes. Thus, our results confirm and extend the recently discovered developmental plasticity of microvascular pericytes, and may open new perspectives to the therapeutic regulation of the renin-angiotensin system.
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