Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney
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Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney. / Gyarmati, Georgina; Shroff, Urvi Nikhil; Riquier-Brison, Anne; Desposito, Dorinne; Ju, Wenjun; Stocker, Sean D; Izuhara, Audrey; Deepak, Sachin; Becerra Calderon, Alejandra; Burford, James L; Kadoya, Hiroyuki; Moon, Ju-Young; Chen, Yibu; Rinschen, Markus M; Ahmadi, Nariman; Lau, Lester; Biemesderfer, Daniel; James, Aaron W; Minichiello, Liliana; Zlokovic, Berislav V; Gill, Inderbir S; Kretzler, Matthias; Peti-Peterdi, János.
In: J CLIN INVEST, Vol. 134, No. 11, e174558, 10.04.2024.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neuronally differentiated macula densa cells regulate tissue remodeling and regeneration in the kidney
AU - Gyarmati, Georgina
AU - Shroff, Urvi Nikhil
AU - Riquier-Brison, Anne
AU - Desposito, Dorinne
AU - Ju, Wenjun
AU - Stocker, Sean D
AU - Izuhara, Audrey
AU - Deepak, Sachin
AU - Becerra Calderon, Alejandra
AU - Burford, James L
AU - Kadoya, Hiroyuki
AU - Moon, Ju-Young
AU - Chen, Yibu
AU - Rinschen, Markus M
AU - Ahmadi, Nariman
AU - Lau, Lester
AU - Biemesderfer, Daniel
AU - James, Aaron W
AU - Minichiello, Liliana
AU - Zlokovic, Berislav V
AU - Gill, Inderbir S
AU - Kretzler, Matthias
AU - Peti-Peterdi, János
PY - 2024/4/10
Y1 - 2024/4/10
N2 - 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 an 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 and 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.
AB - 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 an 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 and 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.
KW - Animals
KW - Mice
KW - Humans
KW - Regeneration
KW - Cell Differentiation
KW - Kidney/metabolism
KW - Neurons/metabolism
KW - Renal Insufficiency, Chronic/pathology
KW - Male
U2 - 10.1172/JCI174558
DO - 10.1172/JCI174558
M3 - SCORING: Journal article
C2 - 38598837
VL - 134
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 11
M1 - e174558
ER -