The role of growth differentiation factor 15 in diabetic kidney injury

PhD ceremony: Ms. M. Mazagová, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: The role of growth differentiation factor 15 in diabetic kidney injury

Promotor(s): prof. R.H. Henning

Faculty: Medical Sciences

The studies presented in this thesis demonstrated a profound role for GDF15 in the development of diabetic nephropathy. GDF15 expression was strongly induced in the glomerulus after induction of diabetes in rats and mice. Further, our study in GDF15 knockout and wild type mice showed that GDF15 preserved tubular function and prevented interstitial damage in both type 1 and type 2 diabetes. However, GDF15 did not protect the glomerulus from sclerosis nor did it prevent albuminuria. Furthermore, pretreatment of vessels (aortas) with GDF15 affected endothelial function resulting in impaired vascular contraction and relaxation. Finally, plasma levels of GDF15 correlated with progression of albuminuria in patients with T2DM. The notion that BMPR2 seems to be involved as a main receptor for GDF15, may facilitate development of novel therapeutic approaches to limit renal damage in diabetic patients.