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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-93570-5 |
| _version_ | 1818346956741672960 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T17:26:30Z |
| format | Article |
| id | doaj.art-0f46efe74446494f8a2827a826347457 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-13T17:26:30Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0f46efe74446494f8a2827a8263474572022-12-21T23:37:11ZengNature PortfolioScientific Reports2045-23222021-07-0111111410.1038/s41598-021-93570-5Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profilesEmily J. Ross0Emily R. Gordon1Hanna Sothers2Roshan Darji3Oakley Baron4Dustin Haithcock5Balabhaskar Prabhakarpandian6Kapil Pant7Richard M. Myers8Sara J. Cooper9Nancy J. Cox10Department of Chemical and Physical Biology, Vanderbilt UniversityHudsonAlpha Institute for BiotechnologyDepartment of Biological Sciences, The University of Alabama in HuntsvilleHudsonAlpha Institute for BiotechnologyHudsonAlpha Institute for BiotechnologyBiomedical and Life Sciences Division, CFD ResearchBiomedical and Life Sciences Division, CFD ResearchBiomedical and Life Sciences Division, CFD ResearchHudsonAlpha Institute for BiotechnologyHudsonAlpha Institute for BiotechnologyDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical CenterAbstract 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.https://doi.org/10.1038/s41598-021-93570-5 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-93570-5 |
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