期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms22105361
关键词
organ-on-a-chip; disease modeling; proximal tubule-on-a-chip; Lowe syndrome; fibrosis; microfluidic; OCRL
资金
- European Union [674983]
- Marie Curie Actions (MSCA) [674983] Funding Source: Marie Curie Actions (MSCA)
Research demonstrates that in a proximal tubule organ on chip model replicating characteristics of Lowe syndrome/Dent II disease, proximal tubule cells lacking OCRL expression upregulate markers associated with epithelial-mesenchymal transition (EMT) and exhibit increased collagen expression and deposition.
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 the underpinning disease mechanisms and to identify and characterise potential drugs and drug targets. Here, we describe a proximal tubule organ on chip model combining a 3D tubule architecture with fluid flow shear stress that phenocopies hallmarks of Lowe syndrome/Dent II disease. We demonstrate the high 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据