Propranolol inhibits endothelial progenitor cell homing: a possible treatment mechanism of infantile hemangioma
Propranolol inhibits endothelial progenitor cell homing: a possible treatment mechanism of infantile hemangioma
复制标题
普萘洛尔抑制内皮祖细胞归巢：婴儿血管瘤的可能治疗机制
DOI：
10.1016/j.carpath.2012.10.001
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发表时间：
2013-05-01
影响因子：
3.7
通讯作者：
Zhao, Yi-Fang
中科院分区：
文献类型：
--
作者：
Zou, Hai-Xiao;Jia, Jun;Zhao, Yi-Fang
背景：普萘洛尔有效治疗婴儿血管瘤，但其作用机制仍知之甚少。虽然普萘洛尔的抗血管生成作用已被证明，一些证据表明，这种治疗剂可能会影响新生血管形成的婴儿血管瘤靶向血管生成。此外，内皮祖细胞归巢到血管瘤病灶在血管生成过程中起重要作用。本研究的目的是探讨普萘洛尔是否通过靶向内皮祖细胞募集抑制婴幼儿血管瘤血管生成方法：内皮祖细胞用不同浓度（0，1，5，10，20，40，60，80，100 μ M）的普萘洛尔处理指定时间（24，48，72 h）。MTT法和台盼蓝染色法检测细胞增殖和活力。通过伤口愈合试验和Boyden小室试验测定细胞迁移。Western blot检测细胞外信号调节激酶、磷酸化细胞外信号调节激酶、Akt和磷酸化Akt的表达水平，探讨普萘洛尔对内皮祖细胞作用的分子机制。结果：普萘洛尔对内皮祖细胞的增殖无明显影响。它抑制基质细胞衍生因子let通过Akt和MAPK途径诱导的内皮祖细胞迁移，并以剂量和时间依赖性方式抑制CXCR4的表达。结论：普萘洛尔抑制基质细胞衍生因子诱导的内皮祖细胞归巢，可能是通过Akt和MAPK途径抑制CXCR4的表达。(C)2013 Elsevier Inc. All rights reserved.
Background: Propranolol effectively treats infantile hemangioma, but its mechanisms of action remain poorly understood. Although the antiangiogenesis role of propranolol has been previously demonstrated, several lines of evidence suggest that this therapeutic agent may affect the neovascular formation in infantile hemangioma by targeting vasculogenesis. In addition, the homing of endothelial progenitor cells to the lesion of infantile hemangioma plays an important role during the process of vasculogenesis. The purpose of this study was to investigate whether propranolol inhibits the vasculogenesis in infantile hemangioma by targeting endothelial progenitor cells recruitment.Methods: Endothelial progenitor cells were treated with different concentrations (0, 1, 5, 10, 20, 40, 60, 80, 100 mu M) of propranolol for indicated times (24, 48, 72 h). Cell proliferation and viability were assessed by MTT assay and trypan blue staining. Cell migration was determined by wound healing assay and Boyden chamber assay. The expression levels of extracellular signal regulated kinase, phospho-extracellular signal regulated kinase, Akt, and phospho-Akt were measured by Western blot analysis to explore the molecular mechanism of propranolol on endothelial progenitor cells. In addition, the expression of CXCR4 was measured by Western blot and reverse transcriptase polymerase chain reaction.Results: Propranolol did not significantly affect the proliferation of endothelial progenitor cells. It inhibited stromal-cell-derived factor let-induced migration of endothelial progenitor cells through the Akt and MAPK pathways and the expression of CXCR4 in a dose- and time-dependent manner. In addition, the expression of CXCR4 was suppressed by propranolol most likely through the Akt and MAPK pathways.Conclusions: Propranolol inhibits stromal-cell-derived factor ice-induced endothelial progenitor cell homing by suppressing the expression of CXCR4 most likely through the Akt and MAPK pathways. (C) 2013 Elsevier Inc. All rights reserved.