Roles of cyclooxygenase-2 in microvascular endothelial cell proliferation induced by basic fibroblast growth factor |
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作者单位: | Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China |
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摘 要: | Background The level of basic fibroblast growth factor (bFGF) increases rapidly after cerebral ischemia. However, the molecular mechanisms for the effects of bFGF on cerebral microvascular endothelial cells (cMVECs) have not yet been fully elucidated. In this study, a murine cMVEC line, bEnd.3, was employed to study the effects of bFGF on cyclooxygenase (COX) expression and its downstream effects in cMVECs. Methods After treatment with bFGF, RT-PCR and Western blotting analyses were carried out to evaluate the changes in COX-2 mRNA and protein expression, respectively. MTT assays were performed to measure cell proliferation. The prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) concentrations in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA). Results COX-2 mRNA and protein expressions in bEnd.3 cells were induced by bFGF in time- and dose-dependent manners. The bFGF-induced COX-2 upregulation led to enhanced PGE2 production by bEnd.3 cells, and this effect was abolished by the selective COX-2 inhibitor NS-398. bFGF also increased VEGF production by bEnd.3 cells, and this effect was blocked by NS-398 and the EP1/2 (PGE2 receptors) antagonist AH6809. Furthermore, exogenous PGE2 increased VEGF production in bend.3 cells, and AH6809 blocked this effect. Conclusion bFGF increases VEGF production in an autocrine manner by increasing COX-2-generated PGE2 in cMVECs and subsequently stimulates MVEC proliferation and angiogenesis.
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关 键 词: | 脑缺血 脑微细胞 成纤维细胞 生长因子 |
Roles of cyclooxygenase-2 in microvascular endothelial cell proliferation induced by basic fibroblast growth factor |
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Authors: | QIAN Rui-zhe YUE Fei ZHANG Guo-ping HOU Li-kun WANG Xin-hong JIN Hui-ming |
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Institution: | QIAN Rui-zhe(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China);YUE Fei(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China);ZHANG Guo-ping(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China);HOU Li-kun(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China);WANG Xin-hong(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China);JIN Hui-ming(Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai 200032, China); |
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Abstract: | Background The level of basic fibroblast growth factor (bFGF) increases rapidly after cerebral ischemia. However, the molecular mechanisms for the effects of bFGF on cerebral microvascular endothelial cells (cMVECs) have not yet been fully elucidated. In this study, a murine cMVEC line, bend.3, was employed to study the effects of bFGF on cyclooxygenase (COX) expression and its downstream effects in cMVECs. Methods After treatment with bFGF, RT-PCR and Western blotting analyses were carried out to evaluate the changes in COX-2 mRNA and protein expression, respectively. Ml-r assays were performed to measure cell proliferation. The prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) concentrations in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA). Results COX-2 mRNA and protein expressions in bEnd.3 cells were induced by bFGF in time- and dose-dependent manners. The bFGF-induced COX-2 upregulation led to enhanced PGE2 production by bEnd.3 cells, and this effect was abolished by the selective COX-2 inhibitor NS-398. bFGF also increased VEGF production by bend.3 cells, and this effect was blocked by NS-398 and the EP1/2 (PGE2 receptors) antagonist AH6809. Furthermore, exogenous PGE2 increased VEGF production in bend.3 cells, and AH6809 blocked this effect. Conclusion bFGF increases VEGF production in an autocrine manner by increasing COX-2-generated PGE2 in cMVECs and subsequently stimulates MVEC proliferation and angiogenesis. |
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Keywords: | cerebral ischemia cerebral microvascular endothelial cell basic fibroblast growth factor cyclooxygenase prostaglandin E2 vascular endothelial growth factor |
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