Angiogenesis,a process by which the preexisting blood vasculature gives rise to new capillary vessels,is associated with a variety of physiologic and pathologic conditions.However,the molecular mechanism underlying th...Angiogenesis,a process by which the preexisting blood vasculature gives rise to new capillary vessels,is associated with a variety of physiologic and pathologic conditions.However,the molecular mechanism underlying this important process remains poorly understood.Here we show that histone deacetylase 6(HDAC6),a microtubule-associated enzyme critical for cell motility,contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells.Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice.The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting.Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization.In addition,microtubule end binding protein 1(EB1)is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures.These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.展开更多
Dear Editor Histone deacetylase 6 （Hdac6） is a mostly cytoplasmic class II HDAC. Many proteins have been identified as substrates of Hdac6. Among them, the most well characterized sub- strate of Hdac6 is a-tubulin. ...Dear Editor Histone deacetylase 6 （Hdac6） is a mostly cytoplasmic class II HDAC. Many proteins have been identified as substrates of Hdac6. Among them, the most well characterized sub- strate of Hdac6 is a-tubulin. Through deacetylating acety- lated lysine 40 in a-tubulin, Hdac6 modulates the acetylation of microtubules （Hubbert et al., 2002）.展开更多
基金the National Natural Science Foundation of China(Grant Nos.30825022 and 90913021)the Fok Ying Tung Education Foundation(Grant No.111036)the National Basic Research Program of China(Grant No.2007CB914802).
文摘Angiogenesis,a process by which the preexisting blood vasculature gives rise to new capillary vessels,is associated with a variety of physiologic and pathologic conditions.However,the molecular mechanism underlying this important process remains poorly understood.Here we show that histone deacetylase 6(HDAC6),a microtubule-associated enzyme critical for cell motility,contributes to angiogenesis by regulating the polarization and migration of vascular endothelial cells.Inhibition of HDAC6 activity impairs the formation of new blood vessels in chick embryos and in angioreactors implanted in mice.The requirement for HDAC6 in angiogenesis is corroborated in vitro by analysis of endothelial tube formation and capillary sprouting.Our data further show that HDAC6 stimulates membrane ruffling at the leading edge to promote cell polarization.In addition,microtubule end binding protein 1(EB1)is important for HDAC6 to exert its activity towards the migration of endothelial cells and generation of capillary-like structures.These results thus identify HDAC6 as a novel player in the angiogenic process and offer novel insights into the molecular mechanism governing endothelial cell migration and angiogenesis.
基金We thank Drs. Xiaohong Zhang, Zhonghua Liu, and Wentao Qiao for help and discussion. This work was supported by the Ministry of Agriculture of China Transgenic Special Program （2009ZX08006-010B, 2009ZX08006-001B）, the National Basic Research Program （973 Program） （Nos. 2011CBA01002 and 2009CB941000）, the National Science and Technology Major Project of China （2012ZX10001-006）, and the Natural Science Foundation of Tianjin, China （No. 14JCYBJC23600）. Dekun Wang, Qingwen Meng, Lihong Huo, Meng Yang, Lingling Wang, Xinyu Chen, Jianchao Wang, Zhiguo Li, Xiaoying Ye, Na Liu, Qiuyan Li, Zhen Dai, Hongsheng Ouyang, Ning Li, Jun Zhou, Lingyi Chen, and Lin Liu declare no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.
文摘Dear Editor Histone deacetylase 6 （Hdac6） is a mostly cytoplasmic class II HDAC. Many proteins have been identified as substrates of Hdac6. Among them, the most well characterized sub- strate of Hdac6 is a-tubulin. Through deacetylating acety- lated lysine 40 in a-tubulin, Hdac6 modulates the acetylation of microtubules （Hubbert et al., 2002）.
