Antibody mediated albuminuria and focal segmental... (2006)

Title Antibody mediated albuminuria and focal segmental glomerulosclerosis in Thy-1.1 transgenic mice
Author Smeets, Bart
Degree grantor Radboud University Nijmegen
Date 2006
Type Doctoral thesis
Publisher [S.l. : s.n.]
Abstract Focal segmental glomerulosclerosis (FSGS) is the hallmark of the glomerular lesion that is characteristically observed in failing kidneys. FSGS is one of the leading causes of renal insufficiency. In this thesis the Thy-1.1 transgenic mouse model was used as a model of FSGS. We particularly evaluated the specific roles of podocytes and parietal epithelial cells (PECs) in the pathogenesis of FSGS. We showed that the FSGS lesions, which are typically observed in the Thy-1.1 model at 3 weeks after antibody injection, were preceded by cellular FSGS lesions that resemble human collapsing FSGS. Characterization of the cellular components of these lesions, revealed that the lesions consisted primarily of proliferating PECs. We concluded that PECs play an important role in the development and progression of FSGS in the Thy-1.1 transgenic mouse. Obviously, these observations in the mouse model prompted the question if PECs are also involved in human FSGS. Thusfar, most studies in patients with collapsing FSGS have attributed the epithelial hyperplasia to dysregulation of podocytes and ensuing proliferation. Therefore, we studied the cellular origin of the proliferating epithelial cells in human idiopathic FSGS and HIV associated collapsing FSGS. From these studies we concluded that the proliferating cells in Bowman's space in human FSGS are derived from PECs. Since the proliferating PECs deposit the newly formed extracellular matrix that leads to scarring, it can be concluded that PECs play an important role in the progression of human FSGS. In addition, we questioned if treatment with captopril could prevent the development of FSGS in the Thy-1.1 transgenic mouse. The data presented in this thesis clearly indicated that captopril reduced albuminuria and almost completely prevented the development of FSGS in our mouse model. Based on our observations we assume that the beneficial effects of captopril are related to its ability to block PEC activation and proliferation.
Persistent Identifier urn:nbn:nl:ui:22-2066/29873
Metadata XML
Repository Radboud University Nijmegen

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