Renin cells in homeostasis, regeneration and immune defence mechanisms

Key Points Renin-expressing cells are evolutionarily conserved and have retained features to contribute to the defence against threats to survival such as bleeding, dehydration, hypotension and/or hypoxia In the embryo, renin-expressing cells populate diverse tissues where they might have a role in tissue morphogenesis and growth; in the developing kidney, they are progenitors for arteriolar and mesangial cells and are crucial for arteriolar branching morphogenesis In adults, cells derived from progenitors that previously expressed renin retain their developmental memory and can regenerate injured glomeruli or re-express renin to achieve blood pressure and fluid–electrolyte homeostasis Renin-expressing cells are linked to other fundamental homeostatic systems, such as the haematopoietic and circulating leukocyte renin–angiotensin systems, through which they might contribute to bone marrow development and the local control of inflammation or infections Renin-expressing cells intersect with erythropoietin-producing cells and are therefore at the crossroads of two key life-sustaining systems involved in the control of fluid volume, perfusion pressure and oxygen delivery to tissues Increasing evidence suggests that renin-expressing cells are involved in a range of physiological processes beyond their traditional role in blood pressure regulation. Here, the authors describe the role of these cells in nephrovascular development, regeneration, oxygen sensing, haematopoiesis and immune responses. An accumulating body of evidence suggests that renin-expressing cells have developed throughout evolution as a mechanism to preserve blood pressure and fluid volume homeostasis as well as to counteract a number of homeostatic and immunological threats. In the developing embryo, renin precursor cells emerge in multiple tissues, where they differentiate into a variety of cell types. The function of those precursors and their progeny is beginning to be unravelled. In the developing kidney, renin-expressing cells control the morphogenesis and branching of the renal arterial tree. The cells do not seem to fully differentiate but instead retain a degree of developmental plasticity or molecular memory, which enables them to regenerate injured glomeruli or to alter their phenotype to control blood pressure and fluid–electrolyte homeostasis. In haematopoietic tissues, renin-expressing cells might regulate bone marrow differentiation and participate in a circulating leukocyte renin