The differentiation of renin expressing cells from the metanephric mesenchyme, in particular the role of precursors, is not well understood. Normally renin expressing cells appear as mural cells of the developing preglomerular arteriolar tree and finally impose as granulated juxtaglomerular cells at the junction between afferent arterioles and glomerular capillaries in the adult kidneys. In states of loss of function of the renin angiotensin-aldosterone-system, however, numerous additional renin expressing cells appear which form multilayered plaque like structures around preglomerular vessels. Since the nature of those ectopic renin cells has not yet been addressed our study aimed to characterize those abundant ectopic renin cells by analyzing the kidneys of mice lacking aldosterone synthase.

We found that these perivascular cell fields contained two apparently distinct cell types. One containing huge electron dense granules staining positive for renin and another one staining positive for type I procollagen. In line, type I and IV collagens were found in the intercellular space of the ectopic renin cell fields. It appeared as if type I procollagen and renin expression was inversely related at the cellular level. In accordance, downregulation of renin expressing cells by high salt diet led to an increase of number of the cells expressing type I procollagen. We conclude from these observations that the cells in the perivascular fields can reversibly switch between procollagen and renin expression, suggesting that type I procollagen expressing cells are precursors of renin cells. Lineage tracing of type I collagen expressing cells in adult wildtype kidneys in fact confirmed that renin expressing cells are descendants of collagen expressing cells. Notably, few of those type I procollagen positive cells were found also in adult wildtype kidneys in the juxtaglomerular area surrounding afferent arterioles at the entrance into the glomerular tuft suggesting a niche of renin cell precursors in this area.