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Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: Inhibition by salvianolic acid B from Salvia miltiorrhiza
Cardiac fibroblasts play the key role in cardiac function and matrix metalloproteinases-9 (MMP-9) is a well known contributor to the development of myocardial remodeling. However, the direct regulation of MMP-9 on the function of cardiac fibroblasts and the underlying mechanism are far from elucidat...
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Published in: | Phytomedicine (Stuttgart) 2011-12, Vol.19 (1), p.13-19 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Cardiac fibroblasts play the key role in cardiac function and matrix metalloproteinases-9 (MMP-9) is a well known contributor to the development of myocardial remodeling. However, the direct regulation of MMP-9 on the function of cardiac fibroblasts and the underlying mechanism are far from elucidation.
In the present research, recombinant protein encoding catalytic domain of MMP-9 (MMP-9 CD) was constructed and the function of neonatal cardiac fibroblasts was investigated by cell proliferation assay, migration assay, picrosirius red assay, multiplex cytokine assay and fibroblast phenotype detection. 200
nM MMP-9 CD stimulated cardiac fibroblasts migration (169.4
±
22.5% versus 100
±
0%,
p
<
0.01), increased collagen synthesis (1.5
±
0.2 fold,
p
<
0.05), up-regulated the secretion of ICAM (574.0
±
40.1 versus 268.5
±
8.6
pg/ml,
p
<
0.01), TNF-α (192.6
±
11.0 versus 14.4
±
1.8
pg/ml,
p
<
0.001), IL-6 (1500.9
±
70.2 versus 323.4
±
40.6
pg/ml,
p
<
0.001) and sVCAM-1 (30.3
±
4.3 versus 7.0
±
0.1
pg/ml,
p
<
0.05) and down-regulated VEGF (436.5
±
148.9 versus 1034.3
±
28.1
pg/ml,
p
<
0.05) significantly with modest effects on proliferation. Accompanying with these regulations, transition of fibroblasts to myofibroblast was confirmed by immunofluorescent stain of α-smooth muscle actin (α-SMA) with MMP-9 CD treatment. Furthermore, salvianolic acid B (SalB) inhibited the effects of MMP-9 CD significantly.
In conclusion, our results provide evidence for a direct influence of MMP-9 on cardiac fibroblast migration, collagen and cytokine secretion, which can be attenuated by SalB. |
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ISSN: | 0944-7113 1618-095X |
DOI: | 10.1016/j.phymed.2011.06.024 |