Role of platelet-derived growth factor (PDGF)-DD in renal fibrosis

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About 5-10% of the general population exhibit moderately to highly impaired renal function (chronic kidney disease: CKD). The universal histological correlate of CKD is renal fibrosis, a process characterized by activation and proliferation of renal mesenchymal cells, e.g. fibroblasts and mesangial cells. We could demonstrate that platelet-derived growth factor (PDGF)–DD, a high-affinity ligand of the PDGF receptor β-chain, is an important factor driving proliferation of glomerular mesangial cells in vitro and in vivo. To date, there is very little additional information on other, in particular pro-fibrotic, roles of PDGF-DD in renal diseases. Data obtained in other organs show that the PDGF system per se is one of the major factors affecting proliferation and activation of mesenchymal cells, i.e. the principal cells driving renal fibrosis. Here, we hypothesize that PDGF-DD plays an important role in renal fibrosis via actions on glomerular mesangial cells and tubulointerstitial fibroblasts. To address this hypothesis, we will use newly developed PDGF-DD knock-out mice and different animal models of renal fibrosis and mesangial stress. We will corroborate these results by in vitro experiments using primary mesangial cells and renal fibroblasts. Potentially, these data could lead to the identification of PDGF-DD as a novel treatment target in renal fibrosis.