Role of fibroblast specific protein 1 expression in the progression of adriamycin-induced glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) is a commonly occurring cause of steroid-resistant nephrotic syndrome and frequently progresses to renal failure. Podocyte epithelial-mesenchymal transition (EMT) is thought to induce podocyte detachment in glomerular diseases, and severe degeneration and shedding of glomerular podocytes plays a major role in the progression of FSGS. We showed that fibroblast specific protein 1 (FSP1), an EMT marker, is strongly expressed in podocytes of FSGS patients, but the significance of podocyte expression of FSP1 to the pathophysiology of FSGS remained unclear. Here, we investigated FSP1 expression in podocytes from mice with adriamycin (ADR)-induced nephropathy, a murine model of FSGS. The number of FSP1-positive (FSP1+) podocytes was increased in ADR-treated mice and positively correlated with the degree of proteinuria and glomerulosclerosis in ADR-treated mice. ADR-induced FSGS and the attendant proteinuria were significantly ameliorated in FSP1 knockout mice as compared to wild type mice. These findings indicate that podocyte expression of FSP1 plays a crucial role in the pathogenesis of FSGS, which makes FSP1 a potential target for treatment of FSGS.