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 perfussion. Here, we discuss briefly the major events that govern the acquisition and maintenace 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 sytem of defense linking the endocrine, the immune and repair responses of the organism.

Figure 1. Inactivation of the RAS in early life leads to marked abnormalities in kidney vascular development

A central feature in all the manipulations is the presence of concentric vascular hypertrophy of the renal arterioles. The lesion does not occur if the renin cells are ablated with diphtheria toxin subunit A (DTA) targeted to the renin gene suggesting that renin cells per se are responsible for the pathology. The same vascular alteration is also seen in humans with renin gene mutations, see text for details. Agt, angiotensinogen; Ren1c−/−, renin gene deletion, ACE−/−, angiotensin converting enzyme deletion,; Agtr1a−/−, Agtr1b−/−, double deletion of angiotensin receptors subtypes A and B. AS−/−, aldosterone synthase KO

Figure 2. Renin cells participate in multiple defense mechanisms

In addition to control of fluid and electrolytes and blood pressure homeostasis, the cells are involved in morphogenetic events and kidney vascular development. They play a role in the regeneration of injured glomeruli and preserve kidney structure. Their presence in hematopoietic tissues suggest a link between the endocrine and immune systems.

Figure 3. Alterations in renin cell fate lead to disease

Conditional deletion of key molecules within renin cells results in in cell fate change leading to renal and systemic pathology. B-RcKO, deletion of the beta-adrenergic receptor; Cx40, connexin 40; VHL, Von Hippel Lindau gene; RBP-J, recombination signal binding protein for immunoglobulin Kappa J. CBF1, human homolog of RBP-J.