High ambient glucose levels modulates the production of MMP-9 and alpha5(IV) collagen by cultured podocytes
| Autor: | Senyan Liu, Yongqiang Li, Haichang Huang, Ya-ling Bai, Jingzi Li, Lizhu Wang, Haiyan Wang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
MAPK/ERK pathway
Collagen Type IV Physiology MAP Kinase Signaling System Matrix metalloproteinase Biology Podocyte Extracellular matrix Diabetic nephropathy Proto-Oncogene Protein c-ets-1 Mice medicine Gelatinase Animals Diabetic Nephropathies RNA Messenger Incubation Cells Cultured Flavonoids Base Sequence Podocytes medicine.disease Molecular biology medicine.anatomical_structure Glucose Biochemistry Matrix Metalloproteinase 9 Signal transduction |
| Zdroj: | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 17(1-2) |
| ISSN: | 1015-8987 |
| Popis: | Recent evidences have demonstrated an important role for glomerular visceral epithelial cell (podocyte) in the development and progression of diabetic nephropathy. We investigated the high-glucose (HG)-triggered signaling pathway and its role in matrix metalloproteinase (MMP) production in murine podocytes. The activity of 92-kDa (MMP-9) gelatinase, but not of 72 kDa (MMP-2), in an HG medium significantly increased during incubation of 2 to 3 days and decreased during incubation of more than 5 days revealed by Gelatin zymography. Opposite to the increases in MMP-9 activity, HG medium produced significant decreases in the protein levels of alpha5(IV) collagen. Changes in MMP-9 activity were associated with the same pattern as MMP-9 mRNA levels in podocytes exposed to HG media. HG medium rapidly activated ERK1/2 MAPK in podocytes. Moreover, ERK1/2 activation was required for HG-induced enhancement of MMP-9 activity and a decrease in the level of alpha5(IV) collagen. HG incubation rapidly induced an increase in the nuclear accumulation of Ets-1 protein. Blocking the ERK pathway suppressed HG-induced expression and nuclear accumulation of transcriptional factor Ets-1, and MMP-9 mRNA expression. We suggest that short- or long-term exposure to HG concentrations increases or decreases MMP-9 production and alpha5(IV) collagen expression in podocytes, this may contribute to the GBM abnormality caused by an imbalance in extracellular matrix (ECM) synthesis and degradation, and may play a critical role in the pathogenesis of proteinuria in diabetic nephropathy. |
| Databáze: | OpenAIRE |
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