Renin-Producing Cells
Renin is produced by juxtaglomerular cells, which are specialized myoepithelioid cells located in the walls of the afferent arterioles at their entrance into the glomeruli. 1, 2, 3
Primary Source: Juxtaglomerular Cells
- Juxtaglomerular cells are the exclusive source of circulating renin and represent highly specialized myoepithelioid granulated cells that line the afferent arterioles where they enter the glomeruli 2, 3, 4
- These cells synthesize preprorenin, which undergoes proteolytic processing to prorenin and then to active renin 1
- Under normal physiological conditions, renin production by juxtaglomerular cells alone suffices to maintain cardiovascular and fluid-electrolyte homeostasis 3
Cellular Plasticity and Recruitment Phenomenon
- When chronic stimulation of renin release occurs (such as during volume depletion, low-salt diet, or antihypertensive therapy), vascular smooth muscle cells along the renal arterioles can transform into renin-producing cells through a process called "recruitment" 5, 3, 6
- Extraglomerular mesangial cells can also undergo reversible metaplastic transformation to produce renin when the body's demand for renin increases 6
- This recruitment involves cells that previously expressed renin during embryonic development re-converting to a renin-producing phenotype 3
Additional Renin Expression Sites
- Renin is also expressed in tubular cells of the distal nephron, overlapping with expression patterns of other genes involved in tubulointerstitial kidney disease 1
- Disease-causing REN gene mutations can result in apoptosis of renin-producing cells in the vas afferens (afferent arterioles) of the glomeruli due to intracellular accumulation of abnormal renin 1
Clinical Significance
- Histologic examination in patients with REN mutations shows reduced renin staining in cells of the juxtaglomerular apparatus 1
- Juxtaglomerular cells of the renin lineage demonstrate remarkable plasticity, capable of migrating into the glomerulus and differentiating into podocytes, epithelial cells, or mesangial cells to restore damaged cells in glomerular disease states 6
- Recent evidence suggests renin-producing cells can undergo an endocrine switch to erythropoietin-producing cells, which may explain the childhood anemia observed in patients with REN mutations 1, 6