Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells
Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells
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DOI：
10.1096/fj.09-134882
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发表时间：
2009-11-01
期刊：
影响因子：
4.8
通讯作者：
Cataltepe, Sule
中科院分区：
文献类型：
--
作者：
Elmasri, Harun;Karaaslan, Cagatay;Cataltepe, Sule
脂肪酸结合蛋白 4 (FABP4) 在维持葡萄糖和脂质稳态中发挥着重要作用。 FABP4 主要被认为是脂肪细胞和巨噬细胞特异性蛋白，但最近的研究表明它可能有更广泛的表达。我们在几种小鼠和人体组织（包括心脏和肾脏）的毛细血管和小静脉的内皮细胞（EC）中发现了强烈的 FABP4 表达。 FABP4 还在成熟人胎盘血管的 EC 和婴儿血管瘤（婴儿和 EC 中最常见的肿瘤）中检测到。在大多数情况下，FABP4 在细胞核和细胞质中均被检测到。 VEGF-A 和 bFGF 处理可显着诱导培养的 EC 中 FABP4 mRNA 和蛋白水平。化学抑制或短发夹 (sh) RNA 介导的 VEGF 受体 2 (R2) 敲低可抑制 VEGF-A 对 FABP4 表达的影响，而 VEGFR1 激动剂、胎盘生长因子 1 和 2 对 FABP4 表达没有影响。 EC 中 FABP4 的敲低在基线条件下以及对 VEGF 和 bFGF 的反应中均显着降低了增殖。因此，FABP4 成为 VEGF/VEGFR2 途径的新靶标，并且是 ECs 中细胞增殖的正调节因子。-Elmasri, H.、Karaaslan, C.、Teper, Y.、Ghelfi, E.、Weng, M.、Ince, T. A.、Kozakewich, H.、Bischoff, J.、Cataltepe, S。脂肪酸结合蛋白 4 是 VEGF 的靶标和细胞增殖的调节因子。内皮细胞。 FASEB J. 23, 3865-3873 (2009)。 www.fasebj.org
Fatty acid binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. FABP4 has been primarily regarded as an adipocyte-and macrophage-specific protein, but recent studies suggest that it may be more widely expressed. We found strong FABP4 expression in the endothelial cells (ECs) of capillaries and small veins in several mouse and human tissues, including the heart and kidney. FABP4 was also detected in the ECs of mature human placental vessels and infantile hemangiomas, the most common tumor of infancy and ECs. In most of these cases, FABP4 was detected in both the nucleus and cytoplasm. FABP4 mRNA and protein levels were significantly induced in cultured ECs by VEGF-A and bFGF treatment. The effect of VEGF-A on FABP4 expression was inhibited by chemical inhibition or short-hairpin (sh) RNA-mediated knockdown of VEGF-receptor-2 (R2), whereas the VEGFR1 agonists, placental growth factors 1 and 2, had no effect on FABP4 expression. Knockdown of FABP4 in ECs significantly reduced proliferation both under baseline conditions and in response to VEGF and bFGF. Thus, FABP4 emerged as a novel target of the VEGF/VEGFR2 pathway and a positive regulator of cell proliferation in ECs.-Elmasri, H., Karaaslan, C., Teper, Y., Ghelfi, E., Weng, M., Ince, T. A., Kozakewich, H., Bischoff, J., Cataltepe, S. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J. 23, 3865-3873 (2009). www.fasebj.org