| Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. | |
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MedLine Citation:
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PMID: 20075196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial-mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of tubular cell EMT. The murine C1.1 tubular epithelial cell line and primary tubular epithelial cells were cultured in activated macrophage-conditioned medium (AMCM) derived from lipopolysaccharide-activated J774 macrophages. MMP-9, but not MMP-2 activity was detected in AMCM. AMCM-induced tubular cell EMT in C1.1 cells was inhibited by broad-spectrum MMP inhibitor (GM6001), MMP-2/9 inhibitor, and in AMCM after MMP-9 removal by monoclonal Ab against MMP-9. AMCM-induced EMT in primary tubular epithelial cells was inhibited by MMP-2/9 inhibitor. MMP-9 induced tubular cell EMT in both C1.1 cells and primary tubular epithelial cells. Furthermore, MMP-9 induced tubular cell EMT in C1.1 cells to an extent similar to transforming growth factor-beta. Transforming growth factor-beta-induced tubular cell EMT in C1.1 cells was inhibited by MMP-2/9 inhibitor. Our in vitro study provides evidence that MMPs, specifically MMP-9, secreted by effector macrophages can induce tubular cell EMT and thereby contribute to renal fibrosis. |
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Authors:
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Thian Kui Tan; Guoping Zheng; Tzu-Ting Hsu; Ying Wang; Vincent W S Lee; Xinrui Tian; Yiping Wang; Qi Cao; Ya Wang; David C H Harris |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-14 |
Journal Detail:
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Title: The American journal of pathology Volume: 176 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-10 Completed Date: 2010-06-07 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1256-70 Citation Subset: AIM; IM |
Affiliation:
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Centre for Transplantation and Renal Research, the University of Sydney at Westmead Millennium Institute, Sydney, NSW 2145 Australia. ttan4526@mail.usyd.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Cell Line Cells, Cultured Culture Media, Conditioned / pharmacology Dipeptides / pharmacology Epithelial Cells / drug effects, enzymology*, pathology* Epithelium / enzymology*, pathology Fibrosis / metabolism Intercellular Signaling Peptides and Proteins / metabolism Kidney Tubules / pathology* Lipopolysaccharides / pharmacology Macrophage Activation / drug effects Macrophages / drug effects, enzymology*, pathology Matrix Metalloproteinase 2 / antagonists & inhibitors, metabolism Matrix Metalloproteinase 9 / antagonists & inhibitors, metabolism* Mesoderm / drug effects, enzymology*, pathology Mice Mice, Inbred BALB C Phenotype Protein Transport / drug effects Recombinant Proteins / pharmacology Ureteral Obstruction / enzymology, pathology |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Culture Media, Conditioned; 0/Dipeptides; 0/GM 6001; 0/Intercellular Signaling Peptides and Proteins; 0/Lipopolysaccharides; 0/Recombinant Proteins; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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