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| Status |
Public on May 21, 2021 |
| Title |
A 3D renal proximal tubule on chip model phenocopies Lowe syndrome and Dent II disease tubulopathy. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Lowe syndrome and Dent II disease are X-linked monogenetic diseases characterised by a renal reabsorption defect in the proximal tubules and caused by mutations in the OCRL gene, which codes for an inositol-5-phosphatase. The life expectancy of patients suffering from Lowe syndrome is largely reduced because of the development of chronic kidney disease and related complications. There is a need for physiological human in-vitro models for Lowe syndrome/Dent II disease to study underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here we describe a proximal tubule organ on chip model combining 3D tubule architecture with fluid flow shear stress, which phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the principal suitability of our in-vitro model for drug target validation. Furthermore, using this model we demonstrate that proximal tubule cells lacking OCRL expression upregulate markers typical for epithelial-mesenchymal transition (EMT) including the transcription factor SNAI2/Slug and show increased collagen expression and deposition, which potentially contributes to interstitial fibrosis and disease progression as observed in Lowe syndrome and Dent II disease.
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| Overall design |
Differential gene expression analysis between OCRL KO_HK2 cells (2 cell lines) vs WT HK2 cells cultured in 3D tubule architecture with fluid flow applying shear stress.
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| Contributor(s) |
Naik S, Ongenaert M, Erdmann K |
| Citation(s) |
34069732 |
| |
| Submission date |
Apr 11, 2021 |
| Last update date |
Aug 20, 2021 |
| Contact name |
Dr. Kai Erdmann |
| Organization name |
University of Sheffield
|
| Department |
Biomedical Science
|
| Street address |
Western Bank
|
| City |
Sheffield |
| State/province |
South Yorkshire |
| ZIP/Postal code |
S10 2TN |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA721193 |
| SRA |
SRP314353 |
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