Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway.
Endothelial cell-fatty acid binding protein 4 promotes angiogenesis: role of stem cell factor/c-kit pathway.
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DOI：
10.1007/s10456-012-9274-0
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发表时间：
2012-09
期刊：
影响因子：
9.8
通讯作者：
Cataltepe, Sule
中科院分区：
文献类型：
--
作者：
Elmasri, Harun;Ghelfi, Elisa;Yu, Chen-wei;Traphagen, Samantha;Cernadas, Manuela;Cao, Haiming;Shi, Guo-Ping;Plutzky, Jorge;Sahin, Mustafa;Hotamisligil, Gokhan;Cataltepe, Sule
脂肪酸结合蛋白4（FABP4）通过其在脂肪细胞和巨噬细胞中的作用在调节葡萄糖和脂质稳态以及炎症中起重要作用。FABP4也在内皮细胞亚群中表达，但其在该细胞类型中的作用尚不清楚。我们发现FABP4缺陷的人脐静脉内皮细胞（HUVECs）表现出对凋亡的敏感性显著增加，以及迁移和毛细血管网络形成减少。来自FABP4 −/−小鼠的主动脉环表现出血管生成发芽减少，这通过FABP4的重建而恢复。FABP4受mTORC 1的强烈调节，并被雷帕霉素抑制。FABP4调节HUVECs中几种重要信号通路的激活，包括下调P38、eNOS和干细胞因子（SCF）/c-kit信号通路。其中，SCF/c-kit途径被发现在减弱FABP4缺陷EC的血管生成活性中具有主要作用，因为提供外源性SCF导致细胞增殖、存活、形态发生和主动脉环发芽的显著恢复。这些数据揭示了内皮细胞FABP4的一种新的促血管生成作用，并表明它可以被开发为与病理性血管生成相关的疾病的潜在靶点。
Fatty acid binding protein 4 (FABP4) plays an important role in regulation of glucose and lipid homeostasis as well as inflammation through its actions in adipocytes and macrophages. FABP4 is also expressed in a subset of endothelial cells, but its role in this cell type is not known. We found that FABP4-deficient human umbilical vein endothelial cells (HUVECs) demonstrate a markedly increased susceptibility to apoptosis as well as decreased migration and capillary network formation. Aortic rings from FABP4−/− mice demonstrated decreased angiogenic sprouting, which was recovered by reconstitution of FABP4. FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin. FABP4 modulated activation of several important signaling pathways in HUVECs, including downregulation of P38, eNOS, and stem cell factor (SCF)/c-kit signaling. Of these, the SCF/c-kit pathway was found to have a major role in attenuated angiogenic activity of FABP4-deficient ECs as provision of exogenous SCF resulted in a significant recovery in cell proliferation, survival, morphogenesis, and aortic ring sprouting. These data unravel a novel pro-angiogenic role for endothelial cell-FABP4 and suggest that it could be exploited as a potential target for diseases associated with pathological angiogenesis.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
在两种血管生成途径中，差异alphav整联蛋白介导的RAS-ERK信号传导。
DOI：
10.1083/jcb.200304105
发表时间：
2003-09-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hood JD;Frausto R;Kiosses WB;Schwartz MA;Cheresh DA
通讯作者：
Cheresh DA
影响因子：
4.8
作者：
Kevil, CG;Orr, AW;Bullard, DC
通讯作者：
Bullard, DC
影响因子：
4.3
作者：
Brevetti, LS;Chang, DS;Messina, LM
通讯作者：
Messina, LM
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR