Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta.
BACKGROUND
Monocyte chemoattractant protein-1 (MCP-1) plays a significant role in the recruitment of monocytes/macrophages in experimental glomerulonephritis (GN). Because recent evidence points to possible profibrogenic effects of leukocyte-derived factors in GN, this study was designed to evaluate the role of the chemokine MCP-1 in the fibrogenesis of experimental GN.


METHODS
Rats with an anti-thy-1-induced GN were treated with a neutralizing antiserum against MCP-1. Glomerular collagen type IV, as a marker of glomerular matrix deposition, was assessed by Northern and Western blotting and immunohistology. Transforming growth factor-beta (TGF-beta), an important mediator of this matrix expansion, was studied by Northern and Western blotting.


RESULTS
The induction of GN resulted in a significant increase of glomerular collagen type IV deposition and TGF-beta synthesis. The neutralization of MCP-1 significantly reduced the enhanced collagen type IV protein synthesis and deposition without affecting collagen mRNA expression. However, both the enhanced transcription and protein synthesis of TGF-beta were inhibited by anti-MCP-1 antiserum in nephritic animals.


CONCLUSIONS
In this model of GN, MCP-1 has a fibrogenic effect through the stimulation of TGF-beta. MCP-1 is thus not only important for the recruitment of inflammatory cells, but also mediates glomerular matrix accumulation.
Schneider
A
A
Department of Medicine, University of Hamburg, Germany.
Panzer
U
U
Zahner
G
G
Wenzel
U
U
Wolf
G
G
Thaiss
F
F
Helmchen
U
U
Stahl
R A
RA
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D018932:Chemokine CCL2 / Q000276:immunology / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007106:Immune Sera / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018932:Chemokine CCL2; D007106:Immune Sera; D016212:Transforming Growth Factor beta; D003094:Collagen