Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The Journal of clinical investigation - (2024) vom: 10. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gyarmati, Georgina [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 12.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1172/JCI174558 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370881621 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a Nephrology | |
| 700 | 1 | |a Shroff, Urvi Nikhil |e verfasserin |4 aut | |
| 700 | 1 | |a Riquier-Brison, Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Desposito, Dorinne |e verfasserin |4 aut | |
| 700 | 1 | |a Ju, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Stocker, Sean D |e verfasserin |4 aut | |
| 700 | 1 | |a Izuhara, Audrey |e verfasserin |4 aut | |
| 700 | 1 | |a Deepak, Sachin |e verfasserin |4 aut | |
| 700 | 1 | |a Becerra Calderon, Alejandra |e verfasserin |4 aut | |
| 700 | 1 | |a Burford, James L |e verfasserin |4 aut | |
| 700 | 1 | |a Kadoya, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Moon, Ju-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yibu |e verfasserin |4 aut | |
| 700 | 1 | |a Rinschen, Markus M |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmadi, Nariman |e verfasserin |4 aut | |
| 700 | 1 | |a Lau, Lester |e verfasserin |4 aut | |
| 700 | 1 | |a Biemesderfer, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a James, Aaron W |e verfasserin |4 aut | |
| 700 | 1 | |a Minichiello, Liliana |e verfasserin |4 aut | |
| 700 | 1 | |a Zlokovic, Berislav |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, Inderbir S |e verfasserin |4 aut | |
| 700 | 1 | |a Kretzler, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Peti-Peterdi, János |e verfasserin |4 aut | |
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