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The relation between altered shear stress-mediated mechanotransduction and loss of glomerular endothelial glycocalyx in the development of albuminuria

Karijosemito, J.J. (2016) The relation between altered shear stress-mediated mechanotransduction and loss of glomerular endothelial glycocalyx in the development of albuminuria. Bachelor's Thesis, Biology.

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Abstract

Albuminuria is a pathological condition, which is characterised by an elevated urinary albumin excretion. Under physiological conditions, the glomeruli are able to prevent albumin passage through the glomerular filtration barrier. An important structure that contributes to albumin retention is the glomerular endothelial glycocalyx. The glycocalyx is a gel-like layer that is localised on the luminal side of glomerular endothelial cells. However, damage to the endothelial glycocalyx leads to passage of albumin through the glomerular wall, which may result in albuminuria. Besides its barrier function, the endothelial glycocalyx also acts as a mechanosensor. Mechanosensors on endothelial cells provide sensing of dynamic blood flow (shear stress), in which mechanotransduction can be induced. Mechanotransduction provides intracellular signalling that is required for regulation of endothelial cell homeostasis. Loss of glycocalyx might result in altered shear stress-mediated mechanotransduction. In addition, impaired mechanotransduction might lead to loss of glycocalyx. Therefore, altered shear stress-mediated mechanotransduction possibly results in albuminuria. This thesis aims to explore the possible relation between altered shear stress-mediated mechanotransduction and loss of glomerular endothelial glycocalyx in the development of albuminuria. Loss of the endothelial glycocalyx is characterised by degradation of heparan sulphate and hyaluronan glycosaminoglycans within the glycocalyx layer. Disturbed shear stress (disturbed blood flow) and disturbed shear stress-induced mechanotransduction can provoke degradation of both glycosaminoglycans. On the other hand, laminar shear stress (normal blood flow) and laminar shear stress-induced mechanotransduction prevent degradation of the glycocalyx. In addition, the endothelial glycocalyx itself also contributes to mechanosensing. However, loss of glycocalyx leads to a decreased blood flow-sensitivity, which causes impaired shear stress-induced mechanotransduction. Subsequently, altered mechanotransduction reinforces degradation of heparan sulphate and hyaluronan. Loss of glycocalyx leads to increased permeability for albumin through the glomerular filtration barrier, which contributes to the development of albuminuria. In conclusion, loss of glomerular endothelial glycocalyx, associated with albuminuria, can be a cause and/or consequence of altered shear stress-mediated mechanotransduction.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 08:24
Last Modified: 15 Feb 2018 08:24
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/14360

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