Glomerular Extracellular Matrix Accumulation in Experimental Anti-GBM Ab Glomerulonephritis
| Autor: | W. W. Tang, Lili Feng, Curtis B. Wilson, David J. Loskutoff |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Platelet-derived growth factor Kidney Glomerulus Antibodies Basement Membrane Extracellular matrix chemistry.chemical_compound Glomerulonephritis Internal medicine Endopeptidases medicine Animals Protease Inhibitors RNA Messenger Growth Substances Basement membrane Extracellular Matrix Proteins biology Glomerular basement membrane Tissue inhibitor of metalloproteinase Immunohistochemistry Molecular biology Extracellular Matrix Rats Fibronectin Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Rats Inbred Lew biology.protein Female Rabbits Plasminogen activator Platelet-derived growth factor receptor |
| Zdroj: | Nephron. 84:40-48 |
| ISSN: | 2235-3186 1660-8151 |
| Popis: | Thickening of the glomerular basement membrane (GBM) results from excessive accumulation of extracellular matrix (ECM) proteins following glomerular injury. We studied the temporal relationship between the expression of growth factors, ECM accumulation, ECM degrading proteinases, and their inhibitors in a rat model of anti-GBM antibody (Ab) glomerulonephritis (GN) by the RNase protection assay and immunohistochemistry. There were two- or fourfold increases in the expression of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) A and B chain mRNAs 4 days after anti-GBM Ab administration. These changes were temporally associated with increased accumulation of α1(III) and α2(IV) collagens, fibronectin, and heparan sulfate proteoglycan along the GBM. The increase in matrix accumulation was associated with little or no increases in the proteinases, urokinase plasminogen activator (u-PA) and transin, respectively. There was a 1.6× increase in the u-PA/28s mRNA ratio on day 4 in rats with anti-GBM Ab GN, but this was not associated with an increase in u-PA biologic activity. By comparison, the mRNAs of the proteinase inhibitors, plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase (TIMP) were 5× greater than that of control rats on day 4. PAI-1 mRNA correlate with increased biologic activity. These data demonstrate a temporal association between TGF-β1 and PDGF expression and matrix accumulation within the GBM in anti-GBM Ab GN. In addition, it suggest that this matrix accumulation results from an imbalance between matrix synthesis and degradation. |
| Databáze: | OpenAIRE |
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