Blockade of osteopontin inhibits glomerular fibrosis in a model of anti-glomerular basement membrane glomerulonephritis.
BACKGROUND
In our rat model for anti-GBM GN, severe fibrosis follows glomerular inflammation. A potential role of extracellular matrix protein osteopontin (OPN) in glomerular fibrosis was investigated.


METHODS
Neutralizing OPN antiserum or control normal serum was injected into the experimental rats at late inflammatory/early fibrotic stage. Glomerular inflammation and fibrosis were determined.


RESULTS
OPN antiserum treatment had little effect on glomerular inflammation. However, the antiserum treatment resulted in a significant reduction in number of fibrotic glomeruli (50% of the controls). Histology observation showed that fibrotic tissue in glomeruli of the antiserum treated rats was mild and poorly developed. OPN antiserum treatment resulted in downregulated glomerular expression of collagen 1α1; collagen deposition in the antiserum treated rats reduced to <30% of that for normal serum controls.


CONCLUSIONS
Neutralization of OPN inhibited progression of fibrosis in vivo when given at early fibrotic stage. Thus, OPN may be a therapeutic target for glomerular fibrosis.
Zhou
Cindy
C
Department of Diagnostic Sciences DB, University of Texas Health Science Center at Houston, USA.
Wu
Jean
J
Torres
Lisa
L
Hicks
John M
JM
Bartkowiak
Todd
T
Parker
Kiana
K
Lou
Ya-Huan
YH
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism* / Q000473:pathology*; D000906:Antibodies / Q000008:administration & dosage; D005260:Female; D005355:Fibrosis / Q000473:pathology*; D005434:Flow Cytometry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*; D023421:Models, Animal; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000097:blood*; D051381:Rats; D011921:Rats, Inbred WKY
D000906:Antibodies; D053495:Osteopontin