Mechanosensing in the Renal Tubule
- 1Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro,” Bari, Italy
- 2Department of Medicine and Health Sciences “Vincenzo Tiberio,” University of Molise, Campobasso, Italy
Abstract
Renal tubular epithelia continuously experience mechanical forces generated by luminal flow and pressure, yet these cues vary dramatically across nephron segments. Despite the declining fluid shear stress from proximal tubule to the collecting duct, the abundance and diversity of mechanosensitive channels increase distally, suggesting that distal segments integrate multiple mechanical inputs rather than fluid shear stress alone. Tubular cells decode at least two spatially segregated cues: tangential drag at the apical surface, sensed by structures such as microvilli and the primary cilium, and circumferential wall tension transmitted to the basolateral domain during flow-driven distension. This multidimensional information is translated into segment-specific physiological responses by compartmentalized Ca2+ signaling, which rapidly couples mechanosensitive ion channels and mechanochemical pathways, including flow-induced ATP release and purinergic receptor activation, to spatially restricted subcellular microdomains. These domain-specific Ca2+ codes control polarity, ion transport, cytoskeletal organization, and transcription, while interfacing with slower hormonal modulatory signals. Importantly, dysfunction of mechanosensitive Ca2+ signaling has direct pathologic relevance: Polycystin mutations disrupt ciliary Ca2+ homeostasis in autosomal dominant polycystic kidney disease, while aberrant mechanotransduction through PIEZO1 and integrin-coupled adhesions supports profibrotic remodeling. This review examines the subcellular domains involved in renal mechanotransduction, focusing primarily on the distal nephron: the apical membrane, the primary cilium, and the basolateral domain, including stretch-activated channels and extracellular matrix–coupled adhesions. It highlights how channels and G protein–coupled receptors shape distinct Ca2+ codes that fine-tune epithelial function along the nephron and identifies key gaps linking mechanosensing to tubular pathophysiology.
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BibTeX
@article{scorza2026mechanosensing,
title = {{Mechanosensing in the Renal Tubule}},
author = {Simona Ida Scorza and Roberta De Zio and Maira Certini and Maria Svelto and Francesco Moccia and Giuseppe Procino and Andrea Gerbino},
journal = {Journal of the American Society of Nephrology : JASN},
year = {2026},
month = jul,
doi = {10.1681/asn.0000001205},
url = {https://doi.org/10.1681/asn.0000001205},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Mechanosensing in the Renal Tubule
AU - Simona Ida Scorza
AU - Roberta De Zio
AU - Maira Certini
AU - Maria Svelto
AU - Francesco Moccia
AU - Giuseppe Procino
AU - Andrea Gerbino
PY - 2026
DA - 2026/07/15
JO - Journal of the American Society of Nephrology : JASN
DO - 10.1681/asn.0000001205
UR - https://doi.org/10.1681/asn.0000001205
AB - Renal tubular epithelia continuously experience mechanical forces generated by luminal flow and pressure, yet these cues vary dramatically across nephron segments. Despite the declining fluid shear stress from proximal tubule to the collecting duct, the abundance and diversity of mechanosensitive channels increase distally, suggesting that distal segments integrate multiple mechanical inputs rather than fluid shear stress alone. Tubular cells decode at least two spatially segregated cues: tangential drag at the apical surface, sensed by structures such as microvilli and the primary cilium, and circumferential wall tension transmitted to the basolateral domain during flow-driven distension. This multidimensional information is translated into segment-specific physiological responses by compartmentalized Ca2+ signaling, which rapidly couples mechanosensitive ion channels and mechanochemical pathways, including flow-induced ATP release and purinergic receptor activation, to spatially restricted subcellular microdomains. These domain-specific Ca2+ codes control polarity, ion transport, cytoskeletal organization, and transcription, while interfacing with slower hormonal modulatory signals. Importantly, dysfunction of mechanosensitive Ca2+ signaling has direct pathologic relevance: Polycystin mutations disrupt ciliary Ca2+ homeostasis in autosomal dominant polycystic kidney disease, while aberrant mechanotransduction through PIEZO1 and integrin-coupled adhesions supports profibrotic remodeling. This review examines the subcellular domains involved in renal mechanotransduction, focusing primarily on the distal nephron: the apical membrane, the primary cilium, and the basolateral domain, including stretch-activated channels and extracellular matrix–coupled adhesions. It highlights how channels and G protein–coupled receptors shape distinct Ca2+ codes that fine-tune epithelial function along the nephron and identifies key gaps linking mechanosensing to tubular pathophysiology.
SN - 1046-6673
SN - 1533-3450
ER -