Generation of Global Metabolomic Profiles of Normal and ADPKD Renal Epithelial Cells Exposed to Fluid Flow-Induced Shear Stress

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Authors
Goulet, Elaina
Ward, Michael
Advisor
Hahn, Alyssa
Editor
Date of Issue
2023-04-28
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Title
Generation of Global Metabolomic Profiles of Normal and ADPKD Renal Epithelial Cells Exposed to Fluid Flow-Induced Shear Stress
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Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a hereditary disease that is the 4th leading cause of renal replacement and failure worldwide. The disease has been linked to mutations of polycystins 1 and 2 in primary cilia in renal epithelial cells under fluid flow shear stress. Cellular pathways become altered due to impaired mechanotransduction, ultimately leading to the formation of renal cysts. The goal of this study was to characterize the metabolic response of ADPKD cell lines under fluid flow-induced shear stress in comparison to healthy renal epithelial cells under static controls. ADPKD cell lines (WT 9-7 and WT 9-12) and healthy renal epithelial cell lines (HK-2) were cultured and exposed to either fluid flow or static conditions and metabolites were extracted for LC-MS analysis. ADPKD cell lines exhibited metabolic changes in response to fluid flow-induced shear stress in comparison to healthy renal epithelial cells, suggestive of dysfunctional mechanotransduction. There were also differences between the two ADPKD cell lines, suggestive of cells being affected differently. This study provides a greater understanding of metabolism in ADPKD pathogenesis for the identification of potential drug targets to slow or ameliorate disease.
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Spring
Department
Biology