The impact of the PDGF-B/PDGFRß signaling cascade for the repopulation of glomerular mesangium after (sever) damage

• Applicant: Dr. Florian Gembardt
• Subject Area: Nephrology
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 288650141

The proposed project shall verify the hypothesis that PDGF-B plays a prominent role for the repopulation of the glomerular mesangium after its destruction in a model of mesangioproliferative glomerulonephritis. Furthermore, the experiments shall identify the impact of juxtaglomerular renin-lineage cells and adjacent PDGF receptor ß (PDGFRß)-positive pericytes on the PDGF-B initiated repopulation.In a previous study, we have illustrated the crucial role of renin-positive cells from the juxtaglomerular apparatus for the regeneration of the damaged mesangium in our model of mesangioproliferative glomerulonephritis. During this repair, the renin-positive cells are entering the glomeruli and gain PDGFRß expression. Since PDGFRß-positive pericytes are important cells for glomerulogenesis, we want to clarify if the pericytes adjacent to the juxtaglomerular apparatus are recruited to the glomeruli after sever mesangial damage and participate in the glomerular repopulation. Additionally, we want to verify the hypothesis that PDGF-B is an essential chemotactic stimulus to recruit such cells. We hypothesize that the renal endothelium is critical source for PDGF-B. To verify our hypothesis, we will use specific antibodies against PDGF-B or PDGFRß and transgenic mice with a cell type-specific deletion of PDGF-B.The combination of the genetic models and pharmacologic interventions in the present proposal, allows us to characterize both, the impact of a local PDGF-B/PDGFRß system (endothelial PDGF-B vs thrombocytic PDGF-B) for mesangial recovery and the role of two different renal cell types (renin-lineage cells vs pericytes) for glomerular repopulation, in detail.

• DFG Programme: Research Grants