The regulation of VPS34 and WNK1 kinase in the proximal tubule of the kidney in health and disease

The proximal tubule (PT) is a high metabolic segment of the kidney. It possesses a reduced glycolytic activity and relies on oxidative mitochondrial metabolism to satisfy its energy demands. This peculiar characteristic makes the PT especially vulnerable to ischemic, hypoxic and metabolic injuries. The function of the PT after glomerular filtration is to reabsorb the number of solutes to avoid excessive loss of vital metabolites but dysfunctions of the proximal tubule can cause excessive excretion of glucose, amino acids and low-molecular weight proteins. The class III phosphoinositide 3-kinase VPS34 and the with-no-lysine [K] (WNK) kinases, have a wide range of functions and are both related to a disease context.The aim of this thesis was to analyze changes in the proximal tubule epithelial cell morphology, function and gene expression using two distinct animal models with conditional knockout of Vps34 and Vhl respectively in the proximal tubule. 



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