Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
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DOI：
10.1074/jbc.m310389200
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发表时间：
2004-01-09
影响因子：
4.8
通讯作者：
Walsh, K
中科院分区：
文献类型：
--
作者：
Ouchi, N;Kobayashi, H;Walsh, K
脂联素是一种脂肪细胞特异性脂肪细胞因子，具有抗动脉粥样硬化和抗糖尿病的特性。在这里，我们研究了脂联素是否在体外和体内调节血管生成过程。脂联素在体外刺激人脐静脉内皮细胞分化为毛细血管样结构，并在迁移实验中起到趋化作用。脂联素促进血管内皮细胞AMP活化蛋白激酶(AMPK)、蛋白激酶Akt/蛋白激酶B和内皮型一氧化氮合酶(ENOS)的磷酸化。显性-负性AMPK或显性-负性Akt信号转导可阻断脂联素诱导的eNOS磷酸化以及脂联素刺激的HUVEC迁移和分化。显性负性AMPK也抑制脂联素诱导的Akt磷酸化，提示AMPK位于Akt的上游。显性负性Akt或磷脂酰肌醇3-激酶抑制剂LY294002可阻断脂联素刺激的Akt和eNOS的磷酸化、迁移和分化，而不改变AMPK的磷酸化。最后，在小鼠Matrigel Plug植入和兔角膜新生血管模型中，脂联素促进了体内血管的生长。这些数据表明，脂联素可以通过促进内皮细胞内AMP激活的蛋白激酶和Akt信号之间的相互作用来刺激新生血管的生长。
Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties. Here, we investigated whether adiponectin regulates angiogenic processes in vitro and in vivo. Adiponectin stimulated the differentiation of human umbilical vein endothelium cells (HUVECs) into capillary-like structures in vitro and functioned as a chemoattractant in migration assays. Adiponectin promoted the phosphorylation of AMP-activated protein kinase ( AMPK), protein kinase Akt/protein kinase B, and endothelial nitric oxide synthesis ( eNOS) in HUVECs. Transduction with either dominant-negative AMPK or dominant-negative Akt abolished adiponectin-induced eNOS phosphorylation as well as adiponectin-stimulated HUVEC migration and differentiation. Dominant-negative AMPK also inhibited adiponectin-induced Akt phosphorylation, suggesting that AMPK is upstream of Akt. Dominant-negative Akt or the phosphatidylinositol 3-kinase inhibitor LY294002 blocked adiponectin-stimulated Akt and eNOS phosphorylation, migration, and differentiation without altering AMPK phosphorylation. Finally, adiponectin stimulated blood vessel growth in vivo in mouse Matrigel plug implantation and rabbit corneal models of angiogenesis. These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.