Pitx2在血管平滑肌细胞分化的早期阶段具有重要功能。
Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation.
作者信息
Shang Yueting, Yoshida Tadashi, Amendt Brad A, Martin James F, Owens Gary K
机构信息
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
出版信息
J Cell Biol. 2008 May 5;181(3):461-73. doi: 10.1083/jcb.200711145.
Abstract
Mechanisms that control vascular smooth muscle cell (SMC) differentiation are poorly understood. We identify Pitx2 as a previously unknown homeodomain transcription factor that is rapidly induced in an in vitro model of SMC differentiation from multipotent stem cells. Pitx2 induces expression of multiple SMC differentiation marker genes by binding to a TAATC(C/T) cis-element, by interacting with serum response factor, and by increasing histone acetylation levels within the promoters of SMC differentiation marker genes. Suppression of Pitx2 reduces expression of SMC differentiation marker genes in the early stages of SMC differentiation in vitro, whereas Prx1, another homeodomain protein, regulates SMC differentiation marker genes in fully differentiated SMCs. Pitx2, but not Prx1, knockout mouse embryos exhibit impaired induction of SMC differentiation markers in the dorsal aorta and branchial arch arteries. Our results demonstrate that Pitx2 functions to regulate the early stages of SMC differentiation.
摘要
控制血管平滑肌细胞（SMC）分化的机制目前仍知之甚少。我们发现Pitx2是一种此前未知的含同源结构域的转录因子，在多能干细胞向SMC分化的体外模型中它能被快速诱导表达。Pitx2通过与TAATC（C/T）顺式元件结合、与血清反应因子相互作用以及提高SMC分化标记基因启动子区域的组蛋白乙酰化水平，来诱导多个SMC分化标记基因的表达。在体外SMC分化的早期阶段，抑制Pitx2会降低SMC分化标记基因的表达，而另一种含同源结构域的蛋白Prx1则在完全分化的SMC中调节SMC分化标记基因。Pitx2基因敲除小鼠胚胎（而非Prx1基因敲除小鼠胚胎）在背主动脉和鳃弓动脉中表现出SMC分化标记诱导受损。我们的结果表明，Pitx2在调节SMC分化的早期阶段发挥作用。
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