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ResearchIn-Press PreviewDevelopmentNephrologyVascular biology Open Access | 10.1172/jci.insight.197709

Renin cells orchestrate a neuro-endocrine microenvironment of the kidney arterial tree in health and disease

Manako Yamaguchi,1 Georgina Gyarmati,2 Liam McLaughlin,3 Hiroki Yamaguchi,1 Jason P. Smith,1 Lucas Ferreira de Almeida,1 Daisuke Matsuoka,1 Alexandre G. Martini,4 Sara M. Wilmsen,5 Sijie Hao,6 Kazuki Tainaka,7 Silvia Medrano,1 Sanjay Jain,3 Janos Peti-Peterdi,2 Maria Luisa S. Sequeira-Lopez,1 and R. Ariel Gomez1

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Yamaguchi, M. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Gyarmati, G. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by McLaughlin, L. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Yamaguchi, H. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Smith, J. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Almeida, L. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Matsuoka, D. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Martini, A. in: PubMed | Google Scholar |

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Wilmsen, S. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Hao, S. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Tainaka, K. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Medrano, S. in: PubMed | Google Scholar |

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Jain, S. in: PubMed | Google Scholar

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Peti-Peterdi, J. in: PubMed | Google Scholar |

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Sequeira-Lopez, M. in: PubMed | Google Scholar |

1Department of Pediatrics Child Health Research Center, University of Virginia School of Medicine, Charlottesville, United States of America

2Department of Physiology and Neuroscience and Department of Medicine, University of Southern California, Los Angeles, United States of America

3Department of Medicine, Washington University School of Medicine, St. Louis, United States of America

4Laboratory of Molecular Pharmacology, University of Brasília, Brasília, Brazil

5Molecular Electron Microscopy Core, University of Virginia School of Medicine, Charlottesville, United States of America

6Advanced Microscopy Facility, University of Virginia School of Medicine, Charlottesville, United States of America

7Department of System Pathology for Neurological Disorders, Niigata University, Niigata, Japan

8Department of Medicine, Washington University School of Medicine, St Louis, United States of America

Find articles by Gomez, R. in: PubMed | Google Scholar

Published July 21, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.197709.
Copyright © 2026, Yamaguchi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 21, 2026 - Version history
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Abstract

Renin cells are essential for survival and serve as key regulators of blood pressure and fluid-electrolyte homeostasis. Their function and identity are dependent on signals from their local microenvironment afforded by neighboring cells and nerves. Whether and how renin cells contribute to the development and maintenance of this microenvironment remains unclear. Because renin cells are rare -0.01 % of kidney cells- conventional histological approaches cannot capture their interaction with nerve fibers and surrounding cells within the nephron and its vasculature. Using high-resolution 3D imaging, cell-specific multicolor reporter mice, single-cell RNA-Seq, and conditional gene deletions, we mapped how renin cells assemble within arterioles and communicate with axon fibers to organize the growth and orientation of the kidney arterioles during development and disease. This co-inductive process is mediated by Ngf produced by renin cell precursors and is necessary for renin cell survival and innervation. Interestingly, renin enzymatic insufficiency elevates Ngf and drives arteriolar hypertrophy with aberrant axon sprouting and hyperinnervation. These findings indicate that renin cells regulate kidney neurovascular development revealing them as active organizers of their local neuroregulatory microenvironment in health and disease.

Graphical Abstract
graphical abstract
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