Fate of Renin Cells During Development and Disease.

Abstract

Although renin cells are crucial for blood pressure homeostasis, little is known about their nature. We now know that renin cells are precursors that appear early and in multiple tissues during embryonic development. They participate in morphogenetic events, vascular development and injury, tissue repair, and regeneration. When confronted to a homeostatic threat, renin cell descendants have the capability to switch the renin gene on or off. This poorly understood switch or molecular memory enables the organism to maintain constancy of the internal milieu and tissue perfusion. Here, we discuss briefly the major events that govern the acquisition and maintenance of renin cell identity and how manipulations that alter the fate of renin cells can lead to serious disease. We also advance the concept that renin cells are at the center of an ancestral system of defense linking the endocrine, the immune, and the repair responses of the organism. The renin–angiotensin system (RAS) is crucial in the regulation of blood pressure and fluid–electrolyte homeostasis.1,2 In the traditional view of the RAS, renin is released by the kidney juxtaglomerular cells, and on reaching the circulation, it acts on its only known substrate, angiotensinogen, produced mainly in the liver to yield angiotensin I (Ang I), a decapeptide and Des-Ang I-angiotensinogen, a large molecule of unclear function. Thereafter, Ang I is hydrolyzed by angiotensin-converting enzyme to yield the octapeptide Ang II, a fast acting and powerful vasoconstrictor that regulates peripheral vascular resistance, renal hemodynamics, and sodium reabsorption via several mechanisms, including the stimulation of aldosterone secretion by the adrenal glands. Most of the known cardiovascular and renal actions of the RAS are achieved by the actions of Ang II on its receptors, mainly AT1 receptors. It should be noted that for the system to operate properly, it needs to respond accurately …