Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response.
Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response.
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DOI：
10.1084/jem.20090121
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发表时间：
2010-08-30
期刊：
影响因子：
--
通讯作者：
Panjwani N
中科院分区：
文献类型：
--
作者：
Markowska AI;Liu FT;Panjwani N
最近的研究表明，碳水化合物结合蛋白Galectin-3是一种新的促血管生成分子。Galectin-3促进血管生成的机制尚不清楚。我们在此证明Galectin-3是血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(BFGF)介导的血管生成反应的媒介。血管生成实验表明，Galectin-3抑制剂β-乳糖和显性阴性Galectin-3在体外可降低血管内皮生长因子和碱性成纤维细胞生长因子介导的血管生成，并且在Galectin-3基因敲除细胞和Gal3−/−动物中血管生成反应减少。整合素αvβ3是主要的Galectin-3结合蛋白，抗αv、-β3和-αvβ3整合素功能阻断抗体显著抑制Galectin-3诱导的血管生成。Galectin-3还可促进整合素αvβ3的聚集，激活粘着斑激酶。GnTV是一种合成Galectin-3的高亲和力糖链配体的酶，它的敲除大大减少了：(A)α与β3整合素上的复杂N-糖链，以及(B)血管内皮生长因子和碱性成纤维细胞生长因子介导的血管生成。综上所述，这些数据提示Galectin-3通过其碳水化合物识别结构域与整合素αvβ3合成的N-糖链结合，进而激活促进新血管生长的信号通路，从而调节血管内皮生长因子和碱性成纤维细胞生长因子介导的血管生成。这些发现对开发基于碳水化合物的抑制血管生成的新型治疗剂具有广泛的意义。
Recent studies have shown that a carbohydrate-binding protein, galectin-3, is a novel pro-angiogenic molecule. The mechanism by which galectin-3 promotes angiogenesis remains unknown. We demonstrate here that galectin-3 is a mediator of vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-mediated angiogenic response. Angiogenesis assays revealed that galectin-3 inhibitors, β-lactose and dominant-negative galectin-3, reduce VEGF- and bFGF-mediated angiogenesis in vitro and that VEGF- and bFGF-mediated angiogenic response is reduced in galectin-3 knockdown cells and Gal3−/− animals. Integrin αvβ3 was identified as the major galectin-3–binding protein and anti-αv, -β3, and -αvβ3 integrin function-blocking antibodies significantly inhibited the galectin-3–induced angiogenesis. Furthermore, galectin-3 promoted the clustering of integrin αvβ3 and activated focal adhesion kinase. Knockdown of GnTV, an enzyme that synthesizes high-affinity glycan ligands for galectin-3, substantially reduced: (a) complex N-glycans on αvβ3 integrins and (b) VEGF- and bFGF-mediated angiogenesis. Collectively, these data suggest that galectin-3 modulates VEGF- and bFGF-mediated angiogenesis by binding via its carbohydrate recognition domain, to the GnTV synthesized N-glycans of integrin αvβ3, and subsequently activating the signaling pathways that promote the growth of new blood vessels. These findings have broad implications for developing novel, carbohydrate-based therapeutic agents for inhibition of angiogenesis.
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影响因子：
8.4
作者：
Brooks, PC
通讯作者：
Brooks, PC
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1083/jcb.200709019
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goetz JG;Joshi B;Lajoie P;Strugnell SS;Scudamore T;Kojic LD;Nabi IR
通讯作者：
Nabi IR
影响因子：
2.9
作者：
ALTIN, JG;PAGLER, EB
通讯作者：
PAGLER, EB
影响因子：
7.8
作者：
Braren, Rickmer;Hu, Huiqing;Kim, Yung Hae;Beggs, Hilary E;Reichardt, Louis F;Wang, Rong
通讯作者：
Wang, Rong