Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles

Abstract The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these...

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Autores principales:	Emily J. Ross, Emily R. Gordon, Hanna Sothers, Roshan Darji, Oakley Baron, Dustin Haithcock, Balabhaskar Prabhakarpandian, Kapil Pant, Richard M. Myers, Sara J. Cooper, Nancy J. Cox
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f46efe74446494f8a2827a826347457
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spelling	oai:doaj.org-article:0f46efe74446494f8a2827a8263474572021-12-02T15:39:58ZThree dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles10.1038/s41598-021-93570-52045-2322https://doaj.org/article/0f46efe74446494f8a2827a8263474572021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93570-5https://doaj.org/toc/2045-2322Abstract The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.Emily J. RossEmily R. GordonHanna SothersRoshan DarjiOakley BaronDustin HaithcockBalabhaskar PrabhakarpandianKapil PantRichard M. MyersSara J. CooperNancy J. CoxNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily J. Ross Emily R. Gordon Hanna Sothers Roshan Darji Oakley Baron Dustin Haithcock Balabhaskar Prabhakarpandian Kapil Pant Richard M. Myers Sara J. Cooper Nancy J. Cox Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
description	Abstract The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.
format	article
author	Emily J. Ross Emily R. Gordon Hanna Sothers Roshan Darji Oakley Baron Dustin Haithcock Balabhaskar Prabhakarpandian Kapil Pant Richard M. Myers Sara J. Cooper Nancy J. Cox
author_facet	Emily J. Ross Emily R. Gordon Hanna Sothers Roshan Darji Oakley Baron Dustin Haithcock Balabhaskar Prabhakarpandian Kapil Pant Richard M. Myers Sara J. Cooper Nancy J. Cox
author_sort	Emily J. Ross
title	Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
title_short	Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
title_full	Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
title_fullStr	Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
title_full_unstemmed	Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
title_sort	three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0f46efe74446494f8a2827a826347457
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Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles

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