Abstract:
:Angiogenesis has become an attractive target for the treatment of certain diseases such as cancer and rheumatoid arthritis. Our previous studies demonstrated that the saponin fraction from Gleditsia sinensis fruits had anti-angiogenic potential, and Gleditsiosides B (GB) was probably the main active constituent. In the present study, we assessed the effect of GB on endothelial cell migration, a crucial event in angiogenesis, and explored the underlying mechanisms. The migration of endothelial cells was assessed by transwell. The expressions of MMP-2/-9 and TIMP-1/-2 were analyzed by Western blotting, and the activities of MMP-2/-9 were detected by gelatin zymography assay. Moreover, migration-related proteins and signaling pathways, including FAK, MAPKs and PI3K/AKT, were analyzed by Western blotting. It was shown that GB, at a concentration of 10 μM without significant cytotoxicity, could effectively abrogate the migration of human umbilical vein endothelial cells (HUVECs) induced by bFGF. GB also inhibited the expression and activity of MMP-2, elevated the expression of TIMP-1, and restrained the phosphorylations of FAK, ERK, PI3K and AKT in a concentration-dependent manner. The findings suggest that GB was able to abrogate the migration of endothelial cells through down-regulating the activation of MMP-2 and FAK via preventing ERK and PI3K/AKT signaling pathways.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Tong B,Lu D,Wei Z,Wang T,Xia Y,Dai Ydoi
10.1016/j.vph.2012.09.006subject
Has Abstractpub_date
2013-01-01 00:00:00pages
118-26issue
1-2eissn
1537-1891issn
1879-3649pii
S1537-1891(12)00189-9journal_volume
58pub_type
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journal_title:Vascular pharmacology
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abstract::Endothelin (ET-1) is chronically elevated in diabetes. However, role of ET-1 in increased oxidative stress in type 2 diabetes is less clear. This study tested the hypotheses that: 1) oxidative stress markers are increased and total antioxidant capacity is decreased in diabetes, and 2) activation of ET(A) receptors med...
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