Once a renin cell, always a renin cell

In an unusual but useful example of cellular flip-flop, a new research study demonstrates that multiple cell types have the ability to temporarily switch into renin-secreting cells when they are needed to stabilize blood pressure. The research, published in the May issue of Developmental Cell, demonstrates that the recruited cells are direct descendants of cells that expressed renin at one time during development.

Renin is a hormone released into the blood by specialized cells in the walls of kidney blood vessels. Renin is released in response to sodium depletion and/or low blood pressure in the blood vessels of the kidneys and it plays a major role in regulating blood pressure generally in the body. Adult mammals can increase circulating renin, when necessary, by increasing the number of renin-synthesizing cells. Dr. R. Ariel Gomez from the University of Virginia and colleagues examined whether the ability of adult cells to synthesize renin was dependent on the cells’ original lineage. The researchers generated mice with a genetic marker that allowed visualization of renin-expressing cells even after the cell had differentiated into a non-renin-secreting cell type. Experimental manipulations known to recruit renin-expressing cells demonstrated that adult cells that were descendants of renin cells retained the capability to make renin when more of the hormone was required to stabilize blood pressure.

The researchers conclude that specific subpopulations of apparently differentiated cells are “held in reserve” to repeatedly respond by de-differentiating and expressing renin in response to stress and then re-differentiating when the crisis has passed. According to Dr. Gomez, “The experiments confirm that recruitment of renin-expressing cells is determined by the developmental history of the cells, which retain the memory to re-express the renin gene under physiological stress. The mice we have generated should be extremely valuable to delete genes specifically in the renin-expressing cell and therefore determine the precise cellular function of those genes independently of systemic influences.”

Maria Luisa S. Sequeira Lopez, Ellen S. Pentz, Takayo Nomasa, Oliver Smithies, and R. Ariel Gomez: “Renin Cells Are Precursors for Multiple Cell Types that Switch to the Renin Phenotype When Homeostasis Is Threatened”

Publishing in Developmental Cell, Volume 6, Number 5, May 2004