摘要：

Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-β. 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-β (TGF-β), 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-β 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-β 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-β. MCP-1 is thus not only important for the recruitment of inflammatory cells, but also mediates glomerular matrix accumulation.

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