Identity of the renin cell is mediated by cAMP and chromatin remodeling: an in vitro model for studying cell recruitment and plasticity

TLDR

The renin‑angiotensin system controls blood pressure and fluid balance, and kidney cells can switch from smooth muscle to renin‑producing endocrine cells when homeostasis is challenged, but the molecular switches that enable this conversion are poorly understood. We created an in‑vitro system that labels renin‑lineage cells with cyan fluorescent protein and actively renin‑transcribing cells with yellow fluorescent protein. The model demonstrates that renin‑lineage cells retain a memory of renin expression through multiple passages and can be re‑activated by cAMP and histone H4 acetylation at the renin gene’s cAMP‑responsive element.

Abstract

The renin-angiotensin system (RAS) regulates blood pressure and fluid-electrolyte homeostasis. A key step in the RAS cascade is the regulation of renin synthesis and release by the kidney. We and others have shown that a major mechanism to control renin availability is the regulation of the number of cells capable of making renin. The kidney possesses a pool of cells, mainly in its vasculature but also in the glomeruli, capable of switching from smooth muscle to endocrine renin-producing cells when homeostasis is threatened. The molecular mechanisms governing the ability of these cells to turn the renin phenotype on and off have been very difficult to study in vivo. We, therefore, developed an in vitro model in which cells of the renin lineage are labeled with cyan fluorescent protein and cells actively making renin mRNA are labeled with yellow fluorescent protein. The model allowed us to determine that it is possible to culture cells of the renin lineage for numerous passages and that the memory to express the renin gene is maintained in culture and can be reenacted by cAMP and chromatin remodeling (histone H4 acetylation) at the cAMP-responsive element in the renin gene.