Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the influence of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) on the release of collagenase type IV activity and the production of extracellular matrix (ECM) molecules using C6 astrocytoma cells in monolayer culture. Collagenase type IV activity was significantly increased in a dose dependent manner in the low cell density group by treatment with FGF-2 and VEGF but significantly decreased in a dose dependent fashion in the high cell density group. These results were corroborated using Western blot technique with an antibody to gelatinase A. Addition of exogenous laminin and fibronectin to the media decreased collagenase type IV activity in a dose dependent fashion with the minimum concentration of 0.1 microgram/ml. Laminin and fibronectin reached a concentration of 0.1 microgram/ml in only the high cell density group after treatment with the growth factors tested. These findings indicate that C6 astrocytoma cells appear to have two regulatory mechanisms for collagenase type IV activity which are dependent on cell density. In a low cell density, C6 astrocytoma cells respond to the dominant effect of FGF-2 and VEGF by increasing the release of collagenase IV activity. In a high cell density collagenase type IV activity is decreased due to it's down regulation by released ECM molecules in response to FGF-2 and VEGF. These regulatory mechanisms may be crucial to the understanding of the coordination of tumor-associated angiogenesis by malignant glial cells.
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PMID:The importance of cell density in the interpretation of growth factor effects on collagenase IV activity release and extracellular matrix production from C6 astrocytoma cells. 982 Nov 6

The aim of the present study is to evaluate the proliferation- and migration-enhancing effects of ginseng and its component, ginsenoside (Rg1) on RSC96 Schwann cells. We investigated the molecular signaling pathways, which include: (1) survival signaling, IGFs-IGFIR-Akt-Bcl2 and proliferative signaling, cell cycle factors and mitogen-activated protein kinase (MAPK) pathways, (2) migrating and anti-scar signaling, FGF-2-uPA-MMPs.We treated RSC96 cells with different concentrations (100, 200, 300, 400, 500 microg ml(-1)) of ginseng and its constituent, Rg1 (5, 10, 15, 20, 25 microg ml(-1)). We observed a proliferative effect in a dose-dependent manner by PCNA western blotting assay, MTT assay, and wound healing test. Furthermore, we also found in the results of western blotting assay, ginseng and Rg1 enhance protein expression of IGF-I pathway regulators, cell cycle controlling proteins, and MAPK signaling pathways to promote the cell proliferation. In addition, ginseng and Rg1 also stimulated the FGF-2-uPA-MMP 9 migrating pathway to enhance the migration of RSC96 Schwann cells. Using MAPK chemical inhibitors, U0126, SB203580, and SP600125, the proliferative effects of ginseng and Rg1 on RSC96 cells were identified to be MAPK signaling-dependent. On the basis of the results, applying appropriate doses of ginseng and Rg1 with biomedical materials would be a potential approach for enhancing neuron regeneration.
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PMID:Proliferation- and migration-enhancing effects of ginseng and ginsenoside Rg1 through IGF-I- and FGF-2-signaling pathways on RSC96 Schwann cells. 1932 80

This study evaluated the proliferation effects of huangqi on neuron regeneration. We investigated the molecular mechanisms, which include: (1) cyclin D1, A, E-cell cycle factors and MAPK signaling proliferation (2) FGF-2-UPA-MMPs migration signaling. After treatment with various Huanqi concentrations (1.25, 12.5, 125, 250 and 500 microg/ml,), we observed that Huanqi can increase Rsc 96 cell proliferation at 12.5 microg/ml (p < 0.01) concentration determined by the MTT and wound healing tests. Examination by RT-PCR and Western blotting assay showed that Huangqi is able to stimulate the mRNA and protein expressions of cyclin D1, A, E, cell cycle controlling proteins and excite ERK and P38 MAPK signaling pathways to promote cell proliferation. Huangqi stimulates the FGF-2-UPA-MMP 9 migration pathway and enhances RSC 96 Schwann cells migration. Using MAPK chemical inhibitors, U0126, SB203580 and SP600125, the proliferative effects of Huangqi on RSC 96 cells were ERK and P38 signaling-dependent. Based on these results, applying an appropriate dose of Huangqi with biomedical materials would be a potential approach to enhancing neuron regeneration.
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PMID:The proliferation and migration effects of huangqi on RSC96 Schwann cells. 1988 54

This study evaluates the proliferative and migrative effects of dangshen on RSC96, Schwann cells. We investigated the molecular signaling pathways, which include: (1) survival signaling, IGFs-IGFIR-Akt-Bcl2 and proliferative signaling, cell cycle factors and MAPK pathways. (2) migrate and anti-scar signaling, FGF-2-uPA-MMPs. After treatment with different concentrations (20 microg/ml, 40 microg/ml, 60 microg/ml, 80 microg/ml, and 100 microg/ml) of dangshen. We observed a dose dependent proliferative effect using PCNA Western blotting assay, MTT assay and the wound healing test. We also found that dangshen stimulates the protein expressions of IGF-I pathway regulators, cell cycle controlling proteins and excites the MAPK signaling pathway regulators ERK and P38. Dangshen even stimulates the FGF-2-uPA-MMP 9 migration pathway in RSC 96 Schwann cells. Using MAPK chemical inhibitors, U0126, SB203580, and SP600125, the proliferative effects of dangshen on RSC 96 cells were identified to be ERK- and P38- dependent. Based on these results, applying an appropriate dose of dangshen with biomedical materials would be a potential approach for enhancing neuron regeneration.
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PMID:Dangshen (Codonopsis pilosula) activates IGF-I and FGF-2 pathways to induce proliferation and migration effects in RSC96 Schwann cells. 2038 31

The epithelial-mesenchymal transition (EMT) of proximal tubular epithelial cells (PTECs) into myofibroblasts contributes to the establishment of fibrosis that leads to end stage renal disease. FGF-2 induces EMT in PTECs. Because the interaction between FGF-2 and its receptor is mediated by heparan sulfate (HS) and syndecans, we speculated that a deranged HS/syndecans regulation impairs FGF-2 activity. Heparanase is crucial for the correct turnover of HS/syndecans. The aim of the present study was to assess the role of heparanase on epithelial-mesenchymal transition induced by FGF-2 in renal tubular cells. In human kidney 2 (HK2) PTEC cultures, although FGF-2 induces EMT in the wild-type clone, it is ineffective in heparanase-silenced cells. The FGF-2 induced EMT is through a stable activation of PI3K/AKT which is only transient in heparanase-silenced cells. In PTECs, FGF-2 induces an autocrine loop which sustains its signal through multiple mechanisms (reduction in syndecan-1, increase in heparanase, and matrix metalloproteinase 9). Thus, heparanase is necessary for FGF-2 to produce EMT in PTECs and to sustain FGF-2 intracellular signaling. Heparanase contributes to a synergistic loop for handling syndecan-1, facilitating FGF-2 induced-EMT. In conclusion, heparanase plays a role in the tubular-interstitial compartment favoring the FGF-2-dependent EMT of tubular cells. Hence, heparanase is an interesting pharmacological target for the prevention of renal fibrosis.
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PMID:Heparanase and syndecan-1 interplay orchestrates fibroblast growth factor-2-induced epithelial-mesenchymal transition in renal tubular cells. 2210 78