Altered expression of fibrogenic growth factors in IgA nephropathy and focal and segmental glomerulosclerosis.
The profile of fibrogenic growth factor expression was assessed in biopsies from 27 patients with IgA nephropathy (IgAN), 14 focal and segmental glomerulsclerosis (FSGS) patients and 8 controls, by immunohistochemistry. Increased platelet-derived growth factor (PDGF)-A and PDGF-B expression was detected in glomeruli and in vascular structures and collapsed tubules in the interstitium. Computer assisted image analysis demonstrated increased glomerular PDGF-A in IgAN (P < 0.05), but not FSGS patients, compared to controls, suggesting an association with mesangial proliferation. PDGF receptors were prominent in areas of mesangial expansion and intertubular fibrosis. Significant increases in interstitial PDGF Receptor beta (PDGFR-beta) were detected for both IgAN (P < 0.01) and FSGS (P < 0.05) patients. Interstitial PDGFR-beta expression was significantly correlated to monocyte/macrophage infiltrate (P < 0.0001). Increased basic fibroblast growth factor (bFGF) expression was observed segmentally in glomeruli, and in areas of tubulointerstitial damage. Higher proportions of patients with FSGS than IgAN had elevated interstitial bFGF (P < 0.005) and PDGF, reflecting the more severe degree of vascular and tubulointerstitial injury in FSGS patients. This study demonstrates distinct patterns of fibrinogenic growth factors in IgAN and FSGS, strongly associated with the severity and type of injury.
Stein-Oakley
A N
AN
Department of Medicine, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia. Alicia.Steine-Oakley@med.monash.edu.au
Maguire
J A
JA
Dowling
J
J
Perry
G
G
Thomsom
N M
NM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D007962:Leukocytes / Q000737:chemistry / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D018950:Lipopolysaccharide Receptors; D010982:Platelet-Derived Growth Factor; D017468:Receptors, Fibroblast Growth Factor; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D017479:Receptors, Platelet-Derived Growth Factor