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.
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.
Authors: Montserrat M Diaz Encarnacion; Gina M Warner; Jingfei Cheng; Catherine E Gray; Karl A Nath; Joseph P Grande Journal: Am J Physiol Renal Physiol Date: 2011-03-02
Authors: Ran Choi; Bo Hwan Kim; Jarinyaporn Naowaboot; Mi Young Lee; Mi Ri Hyun; Eun Ju Cho; Eun Soo Lee; Eun Young Lee; Young Chul Yang; Choon Hee Chung Journal: Exp Mol Med Date: 2011-12-31 Impact factor: 8.718
Authors: O Hertting; A Khalil; G Jaremko; M Chromek; Y-H Li; M Bakhiet; T Bartfai; K Tullus; A Brauner Journal: Clin Exp Immunol Date: 2003-02 Impact factor: 4.330