Cytokines and podocyte injury: the mechanism of fibroblast growth factor 2-induced podocyte injury.

In our study [4], FGF2 and FGF2-neutralizing antibody were administered to animals with PAN nephropathy. After PAN injection, recombinant FGF2 Introduction (group F), FGF2-neutralizing antibody (group M) or the same volume of physiological saline (group C) was Recent studies point to an important role for podocytes injected for 4 days via the tail vein, and the animals in the physiology and pathophysiology of the glomerwere sacrificed on the 25th day after the start of PAN ulus. With regard to the pathogenesis of developing administration. Proteinuria markedly increased in segmental glomerulosclerotic lesions, we [1], as well as group F. The difference in proteinuria excretion was others [2], previously reported that podocytes initially prominent on day 25. When the cell proliferation was detached themselves from the glomerular basement actually assessed by staining with proliferating cell membrane (GBM), leading to the development of nuclear antigen (PCNA) antibody, PCNA-positive adhesions between the denuded membrane and cells clearly increased in group F, while they were Bowman’s capsule. Proliferation of epithelial cells of suppressed in group M. PCNA-positive cells were Bowman’s capsule and an extracellular matrix can be made up mainly of podocytes and epithelial cells of observed in these lesions. Therefore, adhesive lesions Bowman’s capsule. When a comparison was made show morphological changes in the glomerulus after of podocyte damage using an anti-desmin monoclonal podocyte injury. antibody as the marker of podocyte injury, the desmin score was lower in group M than in the other two How does this mechanism contribute to adhesive groups. Adhesive lesions were most common in lesions? group F, while they were less prominent in group M. It is assumed that FGF2 was involved in the formation Our study is designed to find what promotes the of adhesive lesions due to proliferation of epithelial proliferation of epithelial cells in Bowman’s capsule. cells of Bowman’s capsule, since FGF2 administration It has been reported recently that fibroblast growth caused an increase in PCNA-positive epithelial cells of factor 2 (FGF2) has a proliferative effect on cultured Bowman’s capsule and administration of the neutraglomerular epithelial cells [3]. Our study focused on lizing antibody inhibited the formation of adhesive the role of FGF2 in the formation of glomerular glomeruli. Furthermore, these findings indicate the adhesive lesions. Animal models with glomerular possibility that FGF2 will induce the podocyte injury. adhesive lesions were prepared by administering puromycin aminonucleoside (PAN). In normal glomeruli, FGF2 staining was detected at the GBM and in the Why does FGF2 accelerate podocyte injury? mesangial areas. However, an increase of FGF2 staining in the cytoplasm of podocytes was observed in In contrast to mesangial cells and glomerular endothelial cells, podocytes have little proliferative capacity in PAN nephropathy. Furthermore, FGF2 and FGFR 1–4 mRNAs were observed in both podocytes and vivo. The current consensus is that the mature podocyte is able to carry out limited DNA synthesis, but is epithelial cells of Bowman’s capsule. These findings suggest that FGF2 has an important role in the formaunable to undergo cell division [5]. Our study attempted to compare PCNA-positive cells and bromotion of glomerular adhesive lesions. deoxyuridine (BrdU )-positive cells to ascertain the number of podocytes in PAN nephropathy. Also, Correspondence and offprint requests to: T. Sasaki, Division of mesangial cells were studied with a Thy1 GN model, Nephrology, Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan. a model of mesangial proliferative glomerulonephritis.