CXCL14型
XCL2型
CXCL10型
生物
趋化因子
内皮糖蛋白
细胞生物学
趋化因子受体
旁分泌信号
自分泌信号
CCL21型
分子生物学
免疫学
受体
炎症
遗传学
干细胞
川地34
作者
Kira Young,Barbara A. Conley,Diana Romero,Eric Tweedie,Christine F. O’Neill,Ilka Pinz,Louise Brogan,Volkhard Lindner,Lucy Liaw,Calvin P.H. Vary
出处
期刊:Blood
[American Society of Hematology]
日期:2012-11-15
卷期号:120 (20): 4263-4273
被引量:66
标识
DOI:10.1182/blood-2012-07-440784
摘要
BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia (HHT) and vascular remodeling, acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained after BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways. These responses included the up-regulation of the chemokine CXCL12/SDF1 and down-regulation of its receptor CXCR4. Quantitative mass spectrometry identified additional secreted proteins, including the chemokine CXCL10/IP10. RNA knockdown of endoglin and ALK1 impaired SDF1/CXCR4 regulation by BMP9. Because of the association of SDF1 with ischemia, we analyzed its expression under hypoxia in response to BMP9 in vitro, and during the response to hindlimb ischemia, in endoglin-deficient mice. BMP9 and hypoxia were additive inducers of SDF1 expression. Moreover, the data suggest that endoglin deficiency impaired SDF1 expression in endothelial cells in vivo. Our data implicate BMP9 in regulation of the SDF1/CXCR4 chemokine axis in endothelial cells and point to a role for BMP9 signaling via endoglin in a switch from an SDF1-responsive autocrine phenotype to an SDF1 nonresponsive paracrine state that represses endothelial cell migration and may promote vessel maturation.
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