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学科主题临床医学
Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture
Kamio, Koichiro3; Sato, Tadashi2; Liu, Xiangde2; Sugiura, Hisatoshi1; Togo, Shinsaku4; Kobayashi, Tetsu5; Kawasaki, Shin6; Wang, Xingqi2; Mao, Lijun7; Ahn, Youngsoo2; Holz, Olaf8; Magnussen, Helgo8; Rennard, Stephen I.1
关键词Tissue Repair Vascular Endothelial Growth Factor
刊名AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
2008-06-01
DOI10.1152/ajplung.00129.2007
294期:6页:L1226-L1232
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Respiratory System
研究领域[WOS]Physiology ; Respiratory System
关键词[WOS]ENDOTHELIAL GROWTH-FACTOR ; CELL APOPTOSIS ; UP-REGULATION ; EMPHYSEMA ; PROLIFERATION ; SECRETE ; SMOKERS ; DISEASE ; FLUID
英文摘要

Prostacyclin is a short-lived metabolite of arachidonic acid that is produced by several cells in the lung and prominently by endothelial cells. It increases intracellular cAMP levels activating downstream signaling thus regulating vascular mesenchymal cell functions. The alveolar wall contains a rich capillary network as well as a population of mesenchymal cells, i.e., fibroblasts. The current study evaluated the hypothesis that prostacyclin may mediate signaling between endothelial and mesenchymal cells in the alveolar wall by assessing the ability of prostacyclin analogs to modulate fibroblast release of VEGF. To accomplish this study, human lung fibroblasts were cultured in routine culture on plastic support and in three-dimensional collagen gels with or without three prostacyclin analogs, carbaprostacyclin, iloprost, and beraprost, and the production of VEGF was evaluated by ELISA and quantitative real-time PCR. Iloprost and beraprost significantly stimulated VEGF mRNA levels and protein release in a concentration-dependent manner. These effects were blocked by the adenylate cyclase inhibitor SQ-22536 and by the protein kinase A (PKA) inhibitor KT-5720 and were reproduced by a direct PKA activator but not by an activator of exchange protein directly activated by cAMP (Epac), indicating that cAMP-activated PKA signaling mediated the effect. Since VEGF serves to maintain the pulmonary microvasculature, the current study suggests that prostacyclin is part of a bidirectional signaling network between the mesenchymal and vascular cells of the alveolar wall. Prostacyclin analogs, therefore, have the potential to modulate the maintenance of the pulmonary microcirculation by driving the production of VEGF from lung fibroblasts.

语种英语
WOS记录号WOS:000256381000025
引用统计
被引频次:29[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52751
专题北京大学第三临床医学院_风湿免疫科
作者单位1.Juntendo Univ, Sch Med, Dept Resp Med, Tokyo 113, Japan
2.Mie Univ, Grad Sch Med, Dept Internal Med 3, Tsu, Mie, Japan
3.Tokyo Univ Hosp, Dept Resp Med, Tokyo 113, Japan
4.Peking Univ, Hosp 3, Dept Rheumatol, Beijing, Peoples R China
5.Hosp Grosshansdorf, Ctr Pneumol & Thorac Surg, Grosshansdorf, Germany
6.Wakayama Med Univ, Dept Internal Med 3, Wakayama, Japan
7.Nippon Med Sch, Div Pulm Med, Tokyo 113, Japan
8.Univ Nebraska Med Ctr, Omaha, NE 68198 USA
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Kamio, Koichiro,Sato, Tadashi,Liu, Xiangde,et al. Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture[J]. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,2008,294(6):L1226-L1232.
APA Kamio, Koichiro.,Sato, Tadashi.,Liu, Xiangde.,Sugiura, Hisatoshi.,Togo, Shinsaku.,...&Rennard, Stephen I..(2008).Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture.AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY,294(6),L1226-L1232.
MLA Kamio, Koichiro,et al."Prostacyclin analogs stimulate VEGF production from human lung fibroblasts in culture".AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 294.6(2008):L1226-L1232.
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