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.

Neuropilin‐1 regulates renin synthesis in juxtaglomerular cells

“…NaCl depletion is characterized by a rapid increase in the renin secretion rate of existing JG cells. If unsolved, additional recruitment of cells in the afferent arteriole and juxtaglomerular area takes place to increase further the production of renin (Broeker, Schrankl, et al., 2022; Gomez & Sequeira‐Lopez, 2018). In total, 23 Nrp1‐ko and 20 WT animals were subjected to a low‐salt diet in three different experimental settings.…”

“…Renin is a centrepiece of the renin–angiotensin–aldosterone system (RAAS) and blockade strategies targeting the RAAS have led to the development of widely‐used clinical drugs for the treatment of high blood pressure, heart failure, diabetes and chronic kidney disease progression (Zaman et al., 2002). Renin‐producing cells in the kidney are unique because they retain embryonic features such as cellular plasticity (Broeker, Schrankl, et al., 2022). Thus, they can be recruited upon homeostatic challenge or under pathophysiological conditions (Sequeira‐Lopez & Gomez, 2021).…”

Connexin 40-Mediated Regulation of Systemic Circulation and Arterial Blood Pressure

“…The kidney monitors the variations in arterial blood pressure and is involved in the regulation of cardiac output and peripheral vascular resistance by modulating the activity of the renin-angiotensin system [125]. Renin is a protease produced by specialized SMCs that are called juxtaglomerular cells because they are located in the segment of afferent arterioles found just at the entrance of the glomerulus [132, 133]. The secretion rate of renin is coordinated by the juxtaglomerular apparatus, which is a complex structure formed by the spatial organization of different components of the kidney: the part of the afferent arteriole containing renin-secreting cells, the initial segment of the efferent arteriole, the extraglomerular mesangial cells, and the macula densa cells of the distal tubule [125, 133].…”

Salt and Aldosterone – Reciprocal and Combined Effects in Preclinical Models and Humans

“…From an evolutionary perspective the renin angiotensin aldosterone system (RAAS) is designed to preserve sodium in a low-salt (sodium chloride) environment in order to maintain serum osmolality, plasma volume, and blood pressure (reviewed in 1 ). In brief, stimuli such as a drop in renal perfusion pressure or reduced delivery of sodium at the macula densa trigger the secretion of renin from juxtaglomerular cells 2 . Of note, evidence also suggests an independent role for chloride in the regulation of renin release 3 .…”