Renin-expressing cells modulate BP, fluid-electrolyte homeostasis, and kidney development, but remarkably little is known regarding the genetic regulatory network that governs the identity of these cells. Here we compared the gene expression profiles of renin cells with most cells in the kidney at various stages of development as well as after a physiologic challenge known to induce the transformation of arteriolar smooth muscle cells into renin-expressing cells. At all stages, renin cells expressed a distinct set of genes characteristic of the renin phenotype, which was vastly different from other cell types in the kidney. For example, cells programmed to exhibit the renin phenotype expressed Akr1b7, and maturing cells expressed angiogenic factors necessary for the development of the kidney vasculature and RGS (regulator of G-protein signaling) genes, suggesting a potential relationship between renin cells and pericytes. Contrary to the plasticity of arteriolar smooth muscle cells upstream from the glomerulus, which can transiently acquire the embryonic phenotype in the adult under physiologic stress, the adult juxtaglomerular cell always possessed characteristics of both smooth muscle and renin cells. Taken together, these results identify the gene expression profile of renin-expressing cells at various stages of maturity, and suggest that juxtaglomerular cells maintain properties of both smooth muscle and renin-expressing cells, likely to allow the rapid control of body fluids and BP through both contractile and endocrine functions.
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http://dx.doi.org/10.1681/ASN.2011040401 | DOI Listing |
Biomolecules
December 2024
Department of Medicine and Feinstein Institute for Medical Research, Zucker School of Medicine, Hempstead, NY 11549, USA.
Patients carrying APOL1 risk alleles (G1 and G2) have a higher risk of developing Focal Segmental Glomerulosclerosis (FSGS); we hypothesized that escalated levels of miR193a contribute to kidney injury by activating renin-angiotensin system (RAS) in the APOL1 milieus. Differentiated podocytes (DPDs) stably expressing vector (V/DPD), G0 (G0/DPDs), G1 (G1/DPDs), and G2 (G2/DPDs) were evaluated for renin, Vitamin D receptor (VDR), and podocyte molecular markers (PDMMs, including WT1, Podocalyxin, Nephrin, and Cluster of Differentiation [CD]2 associated protein [AP]). G0/DPDs displayed attenuated renin but an enhanced expression of VDR and Wilms Tumor [WT]1, including other PDMMs; in contrast, G1/DPDs and G2/DPDs exhibited enhanced expression of renin but decreased expression of VDR and WT1, as well as other PDMMs (at both the protein and mRNA levels).
View Article and Find Full Text PDFHypertension
February 2025
Department of Physiology (E.M.F., J.G., M.G., K.K., P.C.M., A.H.G., I.V., M.X., A.G., D.G., N.M.M., K.-T.L., K.K.W., D.T.B., G.C.M., M.R.H., J.L.S., J.L.G., C.D.S., P.N.), Medical College of Wisconsin, Milwaukee.
Background: The importance of the brain renin-angiotensin system in cardiovascular function is well accepted. However, not knowing the precise source of renin in the brain has been a limitation toward a complete understanding of how the brain renin-angiotensin system operates.
Methods: Highly sensitive in situ hybridization techniques and conditional knockout mice were used to address the location and function of renin in the brainstem.
Am J Physiol Renal Physiol
January 2025
Division of Pediatric Nephrology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, United States.
Renin is crucial for blood pressure regulation and electrolyte balance, and its expressing cells arise from Forkhead box D1-positive (Foxd1) stromal progenitors. However, factors guiding these progenitors toward renin-secreting cell fate remain unclear. Tcf21, a basic helix-loop-helix (bHLH) transcription factor, is essential in kidney development.
View Article and Find Full Text PDFClin Sci (Lond)
December 2024
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, U.S.A.
Hypertension
September 2024
Department of Pediatrics, Child Health Research Center (J.P.S., R.P., S.M., M.L.S.S.-L., R.A.G.), University of Virginia, Charlottesville, VA.
Background: Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.
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