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ResearchIn-Press PreviewNephrology Open Access | 10.1172/JCI174558
1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
Find articles by Gyarmati, G. in: JCI | PubMed | Google Scholar
1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
Find articles by Burford, J. in: JCI | PubMed | Google Scholar |
1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
Find articles by Kadoya, H. in: JCI | PubMed | Google Scholar
1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
Find articles by Moon, J. in: JCI | PubMed | Google Scholar
1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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1Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America
2Division of Nephrology, University of Michigan, Ann Arbor, United States of America
3Neurobiology, University of Pittsburgh, Pittsburgh, United States of America
4Physiology and Biophysics, University of Southern California, Los Angeles, United States of America
5Nephrology, University of Southern California, Los Angeles, United States of America
6USC Libraries Bioinformatics Service, University of Southern California, Los Angeles, United States of America
7Molecular Medicine, University of Cologne, Cologne, Germany
8Urology, University of Southern California, Los Angeles, United States of America
9Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, United States of America
10Section of Nephrology, Yale University School of Medicine, New Haven, United States of America
11Pathology, Johns Hopkins University, Baltimore, United States of America
12Pharmacology, Oxford University, Oxford, United Kingdom
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Published April 10, 2024 - More info
Tissue regeneration is limited in several organs including the kidney, contributing to the high prevalence of kidney disease globally. However, evolutionary and physiological adaptive responses and the presence of renal progenitor cells suggest existing remodeling capacity. This study uncovered endogenous tissue remodeling mechanisms in the kidney that were activated by the loss of body fluid and salt and regulated by a unique niche of a minority renal cell type called the macula densa (MD). Here we identified neuronal differentiation features of MD cells that sense the local and systemic environment, secrete angiogenic, growth and extracellular matrix remodeling factors, cytokines and chemokines, and control resident progenitor cells. Serial intravital imaging, MD nerve growth factor receptor and Wnt mouse models and transcriptome analysis revealed cellular and molecular mechanisms of these MD functions. Human and therapeutic translation studies illustrated the clinical potential of MD factors including CCN1 as a urinary biomarker and therapeutic target in chronic kidney disease. The concept that a neuronally differentiated key sensory and regulatory cell type responding to organ-specific physiological inputs controls local progenitors to remodel or repair tissues may be applicable to other organs and diverse tissue regenerative therapeutic strategies.