Proteoglycans modulate renal inflammation. Studies on complement and leukocyte recruitment

PhD ceremony: Ms. A. Zaferani, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Proteoglycans modulate renal inflammation. Studies on complement and leukocyte recruitment

Promotor(s): prof. G.J. Navis, prof. M.R. Daha

Faculty: Medical Sciences

Current management of end stage renal disease is based on renal replacement therapy by dialysis or transplantation. Increasing occurrence of renal failure in both native and transplanted kidneys emerges the need for new therapies to stop the progression of the disease. Ischemia/reperfusion (I/R) injury and proteinuria have been shown to be major risk factors in the development of renal failure. Innate immunity plays an important role in the pathogenesis of renal diseases both in native and transplanted kidneys. The complement system forms a major humoral part of the innate immune system. Most of the complement factors interact with proteoglycans (PG) which thus represent docking platforms for complement activation both on cellular membranes and in the extracellular compartment. Therefore, this interaction might be a target for intervention. In this thesis we studied the contribution of proteoglycans in innate immune-derived renal injury in transplantation and native kidney diseases. Based on our findings, we propose a novel mechanism for proteinuria-derived tubular injury via PGs interaction with complement factors. We also showed a novel role for basement membrane PGs in I/R induced renal injury. It is clear that insight in the molecular interactions in renal diseases are important to allow the design of novel strategies for treatment. Our studies provide novel insights in the role of PGs in renal inflammation in relation to innate immune derived injuries. Further research is required to bring these findings closer to application.