PDGF-C Inhibition Reduces Kidney Injury in Mouse Models of Glomerular Disease

A study published in the Journal of the American Society of Nephrology examined whether epithelial platelet-derived growth factor-C (PDGF-C) contributes to crescentic glomerulonephritis and focal segmental glomerulosclerosis (FSGS). Researchers analysed PDGF-C and its receptor PDGFRα in mouse and human kidney tissues. They tested global and kidney epithelial-specific Pdgfc deletion and a neutralizing antibody in murine nephrotoxic nephritis, and pharmacological inhibition in a mouse model of collapsing FSGS. Additional experiments examined parietal epithelial cells (PECs) in vitro.

Under disease conditions, PDGF-C expression increased in PECs and appeared de novo in podocytes. In vitro, PDGF-C promoted PEC proliferation and activation. Across the mouse intervention studies, PDGF-C deficiency or antagonism significantly improved measures of crescent formation, glomerular sclerosis, renal inflammation and kidney function. The transcription factor FOXM1 was identified as a mediator of disease-related PDGF-C expression in PECs.

The findings support epithelial PDGF-C as a contributor to glomerular injury and a potential therapeutic target. However, the intervention evidence is preclinical, and human tissue analyses do not establish treatment benefit. The supplied report provides no sample sizes, numerical effect estimates or detailed kidney function results, limiting assessment of the magnitude and precision of benefit.