Review

Renin cells in homeostasis, regeneration and immune defence mechanisms

Published online:

Abstract

An accumulating body of evidence suggests that renin-expressing cells have developed throughout evolution as a mechanism to preserve blood pressure and fluid volume homeostasis as well as to counteract a number of homeostatic and immunological threats. In the developing embryo, renin precursor cells emerge in multiple tissues, where they differentiate into a variety of cell types. The function of those precursors and their progeny is beginning to be unravelled. In the developing kidney, renin-expressing cells control the morphogenesis and branching of the renal arterial tree. The cells do not seem to fully differentiate but instead retain a degree of developmental plasticity or molecular memory, which enables them to regenerate injured glomeruli or to alter their phenotype to control blood pressure and fluid–electrolyte homeostasis. In haematopoietic tissues, renin-expressing cells might regulate bone marrow differentiation and participate in a circulating leukocyte renin–angiotensin system, which acts as a defence mechanism against infections or tissue injury. Furthermore, renin-expressing cells have an intricate lineage and functional relationship with erythropoietin-producing cells and are therefore central to two endocrine systems — the renin–angiotensin and erythropoietin systems — that sustain life by controlling fluid volume and composition, perfusion pressure and oxygen delivery to tissues. However, loss of the homeostatic control of these systems following dysregulation of renin-expressing cells can be detrimental, with serious pathological events.

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Acknowledgements

The authors thank H. Watanabe, B. Belyea and E. Brown (University of Virginia, Charlottesville, USA) for their comments on the manuscript and figures. Studies were funded by the US National Institutes of Health, Grants DK-096373 and HL-096735 to R.A.G. and DK-091330 and DK-096373 to M.L.S.S.-L.

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  1. Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

    • R. Ariel Gomez
    •  & Maria Luisa S. Sequeira-Lopez

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Both authors contributed equally to researching data for the article, discussion of the content, writing the article and revising and/or editing the manuscript before submission.

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The authors declare no competing financial interests.

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Correspondence to R. Ariel Gomez.

Glossary

Juxtaglomerular cells

A specialized group of renin-producing, myo-epithelioid, granulated cells located at the tip of the afferent arterioles at the entrance to the glomeruli.

Juxtaglomerular apparatus

The functional sensory and responding unit of the renin–angiotensin system; it is composed of the afferent and efferent arterioles, the macula densa and the extraglomerular mesangium.

Plasticity

The ability of cells to switch phenotypes.

Metanephros

The definitive kidney of adult mammals.

Fetal zone

A large, eosinophilic steroidogenic group of cells of the fetal adrenal gland, which is believed to involute after birth.

Mural cells

Cells located within the wall(s) of the renal arterioles, including smooth muscle cells and renin-expressing cells such as juxtaglomerular cells. In larger arteries, adventitial cells such as fibroblasts and perivascular pericytes are sometimes considered mural cells. Although part of the arterial wall, endothelial cells are not usually considered mural cells.

Stromal compartment

One of the three main compartments of the developing kidney; it contains FOXD1+ progenitors of vascular smooth muscle cells, renin-expressing cells, mesangial cells and pericytes as well as SCL+ progenitors of endothelial cells of arteries and arterioles, glomeruli and interstitial capillaries.

Vasculogenesis

De novo, local differentiation and assembly of blood vessels from resident progenitor cells that are usually derived from multiple clones.

Angiogenesis

The formation of new blood vessels, usually by sprouting of new branches from pre-existing vessels. This process usually involves the proliferation and/or elongation of cells from single clones. In the case of arterioles, it is followed by the recruitment of perivascular smooth muscle cells.

Fractal

A shape or structure made of smaller parts or units that repeat themselves and resemble the whole.

Developmental memory

The ability of cells to expressly re-acquire a phenotype previously expressed during development.

Metaplastic transformation

Pathological transformation of one cell type into another not related by lineage.

Hyperplasia

Increase in cell number, usually due to increased cell proliferation.

Neogenesis

De novo expression of a gene (for example, renin) in a cell that has not previously expressed the gene.

Direct transdifferentiation

Transformation of one cell into another without reprogramming into induced pluripotent stem cells.

Erythrocytosis

Increase in red cell mass.

Leukaemic blast cells

Immature forms of white blood cells that fail to differentiate normally and proliferate in an uncontrolled manner, leading to tissue infiltration and, if untreated, death.