Flexible and multifaceted: the plasticity of renin-expressing cells

Abstract

The protease renin, the key enzyme of the renin-angiotensin-aldosterone system, is mainly produced and secreted by juxtaglomerular cells in the kidney, which are located in the walls of the afferent arterioles at their entrance into the glomeruli. When the body's demand for renin rises, the renin production capacity of the kidneys commonly increases by induction of renin expression in vascular smooth muscle cells and in extraglomerular mesangial cells. These cells undergo a reversible metaplastic cellular transformation in order to produce renin. Juxtaglomerular cells of the renin lineage have also been described to migrate into the glomerulus and differentiate into podocytes, epithelial cells or mesangial cells to restore damaged cells in states of glomerular disease. More recently, it could be shown that renin cells can also undergo an endocrine and metaplastic switch to erythropoietin-producing cells. This review aims to describe the high degree of plasticity of renin-producing cells of the kidneys and to analyze the underlying mechanisms.

Keywords: Erythropoietin; Phenotypic transformation; Regeneration; Renal interstitial cells; Renin; Renin–angiotensin–aldosterone system.

Fig. 1

Schematic overview of different aspects of renin-lineage cell plasticity. Renin-lineage cells show a high plasticity and can fulfill different functions in order to maintain renal function, blood pressure, and water and salt balance in the body. Topics highlighted in this review are indicated in bold font

Fig. 2

Interstitial renin-expressing cells on kidney sections of wild-type mice. A Spatial distribution pattern of interstitial renin-expressing cells was visualized with RNAscope, a high resolution in situ hybridization technology. Renin mRNA-expressing cells were highlighted with yellow dots on a kidney section of a wild-type mouse. Interstitial renin mRNA-expressing cells are mainly distributed in the outer medulla and to a lesser extent in the renal cortex. Nuclei were counterstained with DAPI (gray). Scale bar 500 μm. B Medullary detail of a co-RNAscope for renin (green) and PDGFR-β (red) mRNA on a wild-type kidney section. Colocalization of both mRNAs identifies interstitial renin⁺ cells as fibroblast-like cells. Nuclei were counterstained with DAPI (gray). Scale bar 20 μm

Fig. 3

Schematic overview of distinct markers conveying the identity of juxtaglomerular renin cells and of signaling pathways involved in recruitment of extraglomerular (EGM) cells and vascular smooth muscle cells (VSMCs) for renin production. Phenotypic changes accompanying recruitment are also depicted

Fig. 4

Schematic overview illustrating the transformation of juxtaglomerular or interstitial renin⁺ cells into EPO-producing cells