GSE171848
A 3D renal proximal tubule on chip model phenocopies Lowe  syndrome and Dent II disease tubulopathy.
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. 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.