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Pericytes in the renal vasculature: roles in health and disease

Nature Reviews Nephrology volume 14, pages 521–534 (2018)Cite this article

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Abstract

In the dense circulatory system of the kidney, as in all vascularized tissues, pericytes enwrap capillaries and microvessels to regulate angiogenesis, stabilize microvascular networks and control blood flow by vasoconstriction. Specialized renal pericytes known as mesangial cells provide physical support to glomerular capillaries, whereas a subset of juxtaglomerular arteriolar pericytes control the local blood pressure in the glomerulus via contraction and influence systemic blood pressure by secreting renin. Similar to pericytes from many other organs, cultured human renal pericytes give rise to mesenchymal stem/stromal cells, suggesting a role of perivascular cells in renal homeostasis and regeneration. On the other hand, pericytes directly contribute to renal fibrosis, and mesangial cells may have an essential role in the development of glomerulosclerosis and other nephropathies. From their early emergence in the renal embryonic rudiment to their distribution in diverse perivascular niches in the adult organ, we review the anatomy and function of pericytes in the healthy and diseased kidney. Many aspects of the ontogeny, specification and functional specialization of renal pericytes remain elusive. The development of powerful models in the easily accessible and genetically tractable zebrafish will help to uncover the multiple facets of these cells.

Key points

  • Perivascular niches in the kidney are highly heterogeneous, leading to multiple subtypes of perivascular cells with distinct functional roles.

  • Although shown to arise from a forkhead box protein D1 (FOXD1)+ progenitor pool, the precise embryonic origins and developmental signals that determine renal perivascular subpopulations remain undefined or ambiguous.

  • Renal pericytes have key roles in homeostasis; for example, they can regulate blood pressure either directly by their contraction or indirectly by the secretion of renin by certain subpopulations.

  • Renal pericytes can give rise to mesenchymal stem and/or stromal cells, which have shown promise for the treatment of acute kidney injury and chronic kidney disease.

  • Renal pericytes are important in the pathogenesis of kidney disease; they are key to vascular survival, can interact with the immune system and can contribute to glomerular and interstitial fibrosis.

  • Powerful molecular tools for the study of renal pericytes are beginning to emerge in the zebrafish model organism.

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Fig. 1: Renal pericytes.
Fig. 2: Perivascular niches in the kidney.
Fig. 3: Fibrosis of vascular origin in a mouse kidney.
Fig. 4: Renin-expressing mural cells in the adult zebrafish mesonephros.

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Nature Reviews Nephrology thanks R. Kramann and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK

    Isaac Shaw & Bruno Péault

  2. MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

    Isaac Shaw & Jeremy Hughes

  3. University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Edinburgh, UK

    Sebastien Rider, John Mullins & Bruno Péault

  4. Orthopaedic Hospital Research Center and Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Bruno Péault

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Glossary

Angiogenesis

The formation and remodelling of new blood vessels and capillaries from the growth of existing blood vessels.

Mesangial cells

Specialized perivascular cells of the glomerulus that provide structural support to the capillary tuft.

Adventitial cells

Perivascular mesenchymal cells that are located in the tunica adventitia layer of large arteries and veins and can give rise to mesenchymal stem/stromal cells in culture. Molecularly defined as CD45−CD31−CD146−CD34+.

Vasa recta

Bundles of parallel ascending and descending vessels that run from the cortex to the inner medulla of the kidney and form a countercurrent exchange system for water and solutes.

Ureteric bud

(UB). An outgrowth of the mesonephric (or Wolffian) duct that invades the metanephric mesenchyme and undergoes subsequent rounds of branching to give rise to the collecting ducts of the kidney and to the ureter.

Cap mesenchyme

Metanephric mesenchyme that condenses around the tip of the ureteric bud during kidney development and gives rise to cells of the nephron. The cap mesenchyme is characterized by expression of SIX2 and Cbp/p300-interacting transactivator 1 (CITED1).

Renin–angiotensin system

(RAS). A hormonal system of blood pressure regulation. In response to low blood pressure, juxtaglomerular pericytes secrete renin, which converts circulating angiotensinogen to angiotensin I, leading to a cascade that ultimately increases blood pressure.

Vasculogenesis

The de novo formation of new blood vessels via the differentiation of endothelial progenitor cells.

Mesenchymal stem/stromal cells

(MSCs). Plastic adherent cells that express CD105, CD73 and CD90, do not express endothelial and haematopoietic cell markers, and have the ability to differentiate into osteoblasts, adipocytes and chondroblasts in vitro. Pericytes and adventitial cells are in vivo precursors of culture-derived MSCs, which have potential therapeutic properties.

Acute kidney injury

(AKI). An abrupt loss of kidney function in response to a pathological stimulus. AKI is clinically defined as an increase in serum creatinine and/or blood urea nitrogen levels and is characterized by tubular death. Although typically short term and reversible, AKI may predispose to chronic kidney disease.

Chronic kidney disease

(CKD). Long-term, typically irreversible decline in renal function characterized by glomerular and tubulointerstitial fibrosis.

Myofibroblast

Scar-forming cell present in the glomeruli or interstitium of injured kidney that are characterized by the expression of α-smooth muscle actin.

Nitroreductase (NTR) system

A cell-ablation technique in which bacterial nitroreductase enzyme is transgenically expressed in cells of interest, thus sensitizing them to metronidazole.

mem-KillerRed

A membrane-bound protein that when excited by 520–590 nm light produces reactive oxygen species that are toxic to the cell. This protein can be genetically targeted to cells of interest for user-defined spatial and temporal cell ablation in light-accessible tissue.

Bessel beam

A specialized form of laser beam formed either by passing a beam through an axicon lens or by reflecting it off a spatial light modulator. Bessel beams are resistant to scattering and diffraction and therefore can penetrate further into tissue than other types of laser beams.

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Shaw, I., Rider, S., Mullins, J. et al. Pericytes in the renal vasculature: roles in health and disease. Nat Rev Nephrol 14, 521–534 (2018). https://doi.org/10.1038/s41581-018-0032-4

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