Ex vivo studies of renal fibrosis: Insights into mechanisms and treatment targets

Elisabeth Godefrida Dieuwke Stribos

Research output: ThesisThesis fully internal (DIV)

1133 Downloads (Pure)

Abstract

Chronic kidney disease (CKD) is a condition characterized by progressive loss of renal function, often due to advancing scar formation (i.e. fibrosis). However, despite current treatment modalities, CKD can eventually progress to end-stage renal disease where patients are in need of renal replacement therapy (dialysis or renal transplantation). Therefore, novel treatment options are needed to impede or even reverse fibrogenesis in order to halt CKD progression.

The development of novel antifibrotic therapies is being hampered by the lack of translational models that can predict drug efficacy in humans. Fortunately, as delineated in this thesis, precision-cut kidney slices (PCKS) could be the long-coveted translational model needed for drug development. This unique model encompasses all the different cells that constitute an organ and normal architecture is maintained allowing for cell-cell and cell-matrix interactions. The current body of work details the use of PCKS to unravel the pathophysiology of renal fibrogenesis, and in the identification of therapeutic targets.

This thesis provides a detailed characterization of murine and human PCKS as a novel translational model of renal fibrosis, which can be used to study mechanisms of disease and to identify potential therapeutic targets such as tyrosine kinase receptors and the transforming growth factor-β pathway. In addition, the results delineated in this thesis will contribute to the reduction of animal experiments in the field of fibrosis research. PCKS are a great tool in the quest for antifibrotic therapies, which will immensely improve the quality of life of CKD patients.
Translated title of the contributionEx vivo studies van nierfibrose
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Olinga, Peter, Supervisor
  • van Goor, Harry, Supervisor
  • Seelen, Marc, Co-supervisor
  • Mutsaers, Rick, Co-supervisor
Award date11-Dec-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-0241-3
Electronic ISBNs978-94-034-0240-6
Publication statusPublished - 2017

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