Sensing of tubular flow and renal electrolyte transport

Verschuren, Eric H. J.; Castenmiller, Charlotte; Peters, Dorien J.M.; Arjona, Francisco J.; Bindels, René J. M.; Hoenderop, Joost G. J.

doi:10.1038/s41581-020-0259-8

Cited by 46 publications

(57 citation statements)

References 227 publications

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“…Determination of the high resolution PC structure by cryoEM in 2018 provided details as to the assembly of the hetero-oligomeric complex, confirming that incorrect folding and/or trafficking of the receptor to the membrane of the primary cilium could indeed be pathogenic lack of mechanically induced cilia-specific Ca 2+ influx 49 . While primary cilia are one of the possible mechanosensors in renal tubules their role, and that of the PC in flow-induced calcium signaling, is yet to be fully understood under normal physiological conditions and in the context of disease 50,51 .…”

Section: Autosomal Dominant Polycystic Kidney Diseasementioning

confidence: 99%

Ciliopathies and the Kidney: A Review

McConnachie

Stow

Mallett

2021

American Journal of Kidney Diseases

132

107

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Autosomal Dominant Polycystic Kidney Diseasementioning

confidence: 99%

Ciliopathies and the Kidney: A Review

McConnachie

Stow

Mallett

2021

American Journal of Kidney Diseases

132

107

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“…The biomechanical forces within the nephron, including the pressure, circumferential stretch, and fluid shear stress, are integral to several distinct signaling pathways and transport phenomena. Furthermore, tubular flow rates are dynamic and vary dramatically between different nephron segments [122]. Alternations in flow rate occur in concert with changes in glomerular filtration rate (GFR), tubuloglomerular feedback (TGF) via the macula densa, pelvic wall contraction, and reabsorption rates [123][124][125][126][127][128].…”

Section: Physical Stresses and Fluid Flowmentioning

confidence: 99%

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

et al. 2021

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Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.

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“…Furthermore, how to validate the simulation of calcium dynamics by experiments is another challenge, especially for the 3D spatial and temporal distributions. Finally, besides calcium dynamics, there are other signalling pathways involved, including purinergic, ATP, nitric oxide (NO), reactive oxygen species (ROS), and mammalian target of rapamycin (mTOR) signalling pathways [ 144 ]. How to integrate these signalling pathways in the numerical simulations is a non-trivial task.…”

Section: Numerical Simulationsmentioning

confidence: 99%

Primary cilium: a paradigm for integrating mathematical modeling with experiments and numerical simulations in mechanobiology

Peng

Resnick

Young

2021

MBE

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Primary cilia are non-motile, solitary (one per cell) microtubule-based organelles that emerge from the mother centriole after cells have exited the mitotic cycle. Identified as a mechanosensing organelle that responds to both mechanical and chemical stimuli, the primary cilium provides a fertile ground for integrative investigations of mathematical modeling, numerical simulations, and experiments. Recent experimental findings revealed considerable complexity to the underlying mechanosensory mechanisms that transmit extracellular stimuli to intracellular signaling many of which include primary cilia. In this invited review, we provide a brief survey of experimental findings on primary cilia and how these results lead to various mathematical models of the mechanics of the primary cilium bent under an external forcing such as a fluid flow or a trap. Mathematical modeling of the primary cilium as a fluid-structure interaction problem highlights the importance of basal anchorage and the anisotropic moduli of the microtubules. As theoretical modeling and numerical simulations progress, along with improved state-of-the-art experiments on primary cilia, we hope that details of ciliary regulated mechano-chemical signaling dynamics in cellular physiology will be understood in the near future.

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Sensing of tubular flow and renal electrolyte transport

Cited by 46 publications

References 227 publications

Ciliopathies and the Kidney: A Review

Ciliopathies and the Kidney: A Review

Tissue Chips and Microphysiological Systems for Disease Modeling and Drug Testing

Primary cilium: a paradigm for integrating mathematical modeling with experiments and numerical simulations in mechanobiology

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