PMID- 10411686 OWN - NLM STAT- MEDLINE DCOM- 19990803 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 56 IP - 1 DP - 1999 Jul TI - Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta. PG - 135-44 AB - 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. FAU - Schneider, A AU - Schneider A AD - Department of Medicine, University of Hamburg, Germany. FAU - Panzer, U AU - Panzer U FAU - Zahner, G AU - Zahner G FAU - Wenzel, U AU - Wenzel U FAU - Wolf, G AU - Wolf G FAU - Thaiss, F AU - Thaiss F FAU - Helmchen, U AU - Helmchen U FAU - Stahl, R A AU - Stahl RA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Chemokine CCL2) RN - 0 (Immune Sera) RN - 0 (Transforming Growth Factor beta) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Cell Movement/physiology MH - Chemokine CCL2/immunology/*physiology MH - Collagen/*metabolism MH - Glomerulonephritis/*metabolism/pathology/physiopathology MH - Immune Sera/immunology MH - Macrophages/physiology MH - Male MH - Monocytes/physiology MH - Rats MH - Rats, Wistar MH - Transforming Growth Factor beta/*physiology EDAT- 1999/07/20 00:00 MHDA- 1999/07/20 00:01 CRDT- 1999/07/20 00:00 PHST- 1999/07/20 00:00 [pubmed] PHST- 1999/07/20 00:01 [medline] PHST- 1999/07/20 00:00 [entrez] AID - S0085-2538(15)46269-6 [pii] AID - 10.1046/j.1523-1755.1999.00543.x [doi] PST - ppublish SO - Kidney Int. 1999 Jul;56(1):135-44. doi: 10.1046/j.1523-1755.1999.00543.x.