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Renal heparan sulfate proteoglycans

A double edged sword
PhD ceremony:Mr D.T. (Ditmer) Talsma
When:January 10, 2018
Start:12:45
Supervisors:prof. dr. C.A. Stegeman, prof. dr. M.R. Daha
Co-supervisors:dr. J. van den Born, dr. M.A.J. Seelen
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

Renal heparan sulfate proteoglycans

Inflammation plays an important role in the pathophysiology of many renal diseases. Processes which play an important role in inflammation are, amongst others, migration of inflammatory cells across the endothelial barrier and the complement system, a protein cascade. In the past couple of years it has been shown that heparan sulfates have an important function in these inflammatory processes. Heparan sulfates consist of a protein core with saccharide chains attached to them and are present on all cells and basement membrane, which means also on endothelial cells. In this thesis we show that dysfunctional heparan sulfates on the endothelial cells result in a reduced inflammatory response in diabetic nephropathy. Moreover, we demonstrate that the heparan sulfates on the endothelial basement membranes have an important function in the migration of inflammatory cells. Treatment aiming for the interaction between heparan sulfates and the inflammatory system in a chronic transplant dysfunction model results in a reduced inflammatory response but fails to show improved transplant function. Besides cellular inflammation, we also investigated inhibition of the complement system by heparan sulfates. We showed that heparin, a polysaccharide derived from heparan sulfate, can inhibit the lectin route of complement. We also demonstrate that Salp20, a tick protein, can inhibit the alternative pathway of complement.The discoveries in this thesis can form the basis for new therapeutic entities in the treatment of renal diseases. However our results are only the beginning and more research should be done to confirm the clinical potency of these results.