Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy.
Podocyte injury is believed to contribute to glomerulosclerosis in membranous nephropathy. To identify the factors involved, we investigated the effects of basic fibroblast growth factor (bFGF), a cytokine produced by podocytes, on rats with membranous nephropathy (passive Heymann nephritis [PHN]). All rats received a daily i.v. bolus of 10 microg bFGF or vehicle from days 3-8 after PHN induction. In proteinuric PHN rats on day 8, bFGF injections further increased proteinuria. Podocytes of bFGF-injected PHN rats showed dramatic increases in mitoses, pseudocyst formation, foot process retraction, focal detachment from the glomerular basement membrane, and desmin expression. bFGF injections in PHN rats did not alter antibody or complement deposition or glomerular leukocyte influx. bFGF-injected PHN rats developed increased glomerulosclerosis when compared with control PHN rats. Also, bFGF induced proteinuria and podocyte damage in rats injected with 10% of the regular PHN-serum dose. None of these changes occurred in bFGF-injected normal rats, complement-depleted PHN rats or rats injected with 5% of the regular PHN serum dose. These divergent bFGF effects were explained in part by upregulated glomerular bFGF receptor expression, induced by PHN serum. Thus, bFGF can augment podocyte damage, resulting in increased glomerular protein permeability and accelerated glomerulosclerosis. This bFGF action is confined to previously injured podocytes. Release of bFGF from glomerular sources (including podocytes themselves) during injury may represent an important mechanism by which podocyte damage is enhanced or becomes self sustained.
Floege
J
J
Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
Kriz
W
W
Schulze
M
M
Susani
M
M
Kerjaschki
D
D
Mooney
A
A
Couser
W G
WG
Koch
K M
KM
D000818:Animals; D017209:Apoptosis; D003893:Desmin / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity*; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D003893:Desmin; D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2